11-06-2012 09:22 Exclusive interview from Dr Jean Bennett MD, Ph.D. (FM Kirby Professor of Ophthalmology at the University of Pennsylvania School of Medicine, USA) and Albert Maguire MD (Associate Professor of Ophthalmology Univesity of Pennsylvania School of Medicine, Physician - Children's Hospital of Philadelphia) on Gene Therapy for treatment of Severe Eye Disease. Interview, November 2009.

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Gene Therapy for treatment of Severe Eye Disease - http://www.pointsdevue.net - Essilor - Video

Newswise A study led by Vanderbilt-Ingram Cancer Center (VICC) investigators has identified a gene expression pattern that may explain why chemotherapy prior to surgery isnt effective against some tumors and suggests new therapy options for patients with specific subtypes of breast cancer.

The study by lead author Justin Balko, Pharm.D., Ph.D., was published online June 10, 2012 in Nature Medicine in advance of print publication. Balko is a postdoctoral fellow in the laboratory of Carlos L. Arteaga, M.D., associate director for Clinical Research and director of the Breast Cancer Program at VICC, who led the study.

About 30 percent of breast cancer patients have a pathological complete response when chemotherapy is used to shrink tumors prior to surgery. However, many patients still have residual cancer in the breast after neoadjuvant chemotherapy (NAC) is completed. These patients are at a higher risk of cancer recurrence and death.

The investigators suspected that profiling tumors after neoadjuvant chemotherapy would identify genes associated with resistance to this form of treatment. They studied gene expression patterns in 49 breast tumors obtained during surgery after four months of NAC.

They identified and analyzed specific groups of genes associated with high-grade, chemotherapy-resistant tumors, labeling their 244 unique genes the CLUSTER signature, and combined this panel with previously identified gene signatures to search for distinctive patterns of behavior.

The investigators found that low concentrations of dual specificity protein phosphatase 4 (DUSP4) is strongly correlated with faster tumor cell growth following neoadjuvant chemotherapy. Low DUSP4 was also correlated with a type of breast cancer known as basal-like breast cancer (BLBC). DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation were also higher in BLBC relative to other breast cancer subtypes.

When DUSP4 was present, chemotherapy was effective against cancer cells, whereas when DUSP4 was experimentally deleted, there was a much lower response to chemotherapy.

These data suggest that cells with low DUSP4 expression are enriched during NAC and that low DUSP4 expression in residual resected breast tumors is a potential biomarker for drug resistance and a high likelihood of tumor recurrence, said Balko.

The group also hypothesized that DUSP4 may be a potential biomarker for response to drugs that inhibit the MEK kinase. Using DUSP4-deficient tumors established in mice, they compared treatment with the chemotherapy drug docetaxel, with and without the MEK inhibitor selumetinib. This study showed that the combination was much more effective than docetaxel alone at eliminating the mouse tumors.

These data support exploratory clinical trials combining chemotherapy and MEK inhibitors in patients with DUSP-deficient basal-like breast cancer, said Balko.

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Study Identifies Genes Linked to Resistance to Breast Cancer Chemotherapy

ScienceDaily (June 11, 2012) Why do some cancers spread rapidly to other organs and others don't metastasize? A team of UNC researchers led by Norman Sharpless, MD, have identified a key genetic switch that determines whether melanoma, a lethal skin cancer, spreads by metastasis.

Treating melanoma is extremely challenging. The cancer spreads rapidly and to sites in the body that are remote from the original cancer site. Melanoma is the most deadly form of skin cancer, and advanced melanoma kills more than 8600 Americans each year. It is the most common form of cancer in young adults, aged 25-29 and the incidence of people under 30 developing melanoma is increasing fast -- more than 50 percent in young women since 1980.

In a paper published June 11 in the journal Cancer Cell, a team from UNC Lineberger Comprehensive Cancer Center demonstrates that inactivating a gene called LKB1 (or STK11) causes non-aggressive melanoma cells to become highly metastatic when tested in a variety of models using tumors from humans and mice. While Sharpless and his colleagues showed a role for LKB1 inactivation in lung cancer metastasis, the effects of LKB1 loss on melanoma spread is even more dramatic.

"Although we are not totally certain how LKB1 loss promotes metastasis in multiple cancer types, one important effect is the loss of LKB1 starts a chain reaction, activating a family of proteins called SRC kinases, which are known to drive metastasis," said Sharpless, who is associate director for translational research at UNC Lineberger.

"Loss of LKB1 occurs in about 30 percent of lung cancer and 10 percent of melanoma, and ongoing studies at UNC and elsewhere will determine if these LKB1 deficient tumors have a worse prognosis. These data suggest LKB1 deficient cancers will be more likely to metastasize, and therefore more likely to be incurable."

"The work is exciting because the laboratory model reliably replicates distant metastases, helping us better understand what treatments may work for melanoma that has spread. While several targeted drugs have recently been approved by the FDA for metastatic disease, these targeted mutations don't indicate whether the disease is likely to metastasize," said Stergios Moschos, MD, clinical associate professor of hematology/oncology. Moschos works in the area of drug development for melanoma but was not involved in this research project.

Other members of the research team from UNC-Chapel Hill include Wenjin Liu, PhD; Kimberly Monahan, PhD; and Jessica Sorrentino, BS, from the department of genetics; Adam Pfefferle, BS, and Ryan Miller, MD, from the department of pathology and laboratory medicine; Keefe Chan, PhD, David Roadcap, PhD, and James Bear, PhD; from the department of cell and developmental biology; David Ollila, MD, from the division of surgical oncology and endocrine surgery; and Charles Perou, PhD, of the departments of genetics and pathology and the Carolina Genome Sciences Center. Dr. Miller, Bear, Ollila, and Perou are also members of UNC Lineberger Comprehensive Cancer Center and Dr. Bear is a Howard Hughes Medical Institute investigator.

Kwok-Kin Wong, MD PhD, from the Dana-Farber Cancer Institute and Harvard Medical School and Diego Castrillon, MD PhD, from the University of Texas Southwestern Medical Center also contributed to the finding.

The research was funded by the National Cancer Institute and the NCI's Mouse Model of Human Cancer Consortium (MMHCC), the National Institute on Aging and the National Institute of Environmental Health Sciences (all part of the National Institutes of Health.

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Gene inactivation drives spread of melanoma

ScienceDaily (June 11, 2012) Presence of normal p53, a tumor suppressor gene, instead of a mutated version, makes breast cancer chemotherapy with doxorubicin less effective. The preclinical study led by MD Anderson scientists was published June 11 in the journal Cancer Cell.

The research, which challenges the existing paradigm, is another step closer to personalized cancer medicine for breast cancer.

"It's really important to understand the genetic defects a tumor cell has before we treat it," said lead author Guillermina Lozano, Ph.D., professor and chair of the Department of Genetics. "What we learned here is the complete opposite of what we expected. We thought tumors would respond better to treatment if the p53 gene were normal. But the opposite was true, and for a really interesting reason."

Lozano said the research in mouse models showed that non-mutated p53 halted cell division, initiating a senescence (cell aging) process that allowed cells to survive. These senescent cells produce factors that stimulate adjacent cells to grow, fueling the relapse. Mutant p53 cells do not arrest and proceed through the cell cycle into cell division with broken chromosomes caused by the chemotherapy.

"That's a signal for the cell to die," she said. "It can't go any farther."

P53 status crucial to predicting response

The tumor suppressor p53 is mutated or inactivated in the majority of cancers, and about one-third of breast cancers have mutations in the gene. It has long been thought that normal p53 results in a better chemotherapy response, but the evidence in breast cancer has been conflicting.

According to the National Cancer Institute, about 227,000 women in the United States are diagnosed with breast cancer each year.

In this study, doxorubicin-treated p53 mutant tumor cells did not stop cell proliferation, leading to abnormal mitoses and cell death, whereas tumors with normal p53 arrested, avoiding mitotic catastrophe.

"There are a lot of data out there on responses of women to doxorubicin and other drugs that break DNA," Lozano said. "The response rates were mixed, and we never understood the difference. Now we understand that we need to know the p53 status to predict a response."

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Normal gene hinders breast cancer chemotherapy

Mutated tumor suppressor gene p53 leads to better results

Newswise HOUSTON - Presence of normal p53, a tumor suppressor gene, instead of a mutated version, makes breast cancer chemotherapy with doxorubicin less effective. The preclinical study led by MD Anderson scientists was published today in the journal Cancer Cell.

The research, which challenges the existing paradigm, is another step closer to personalized cancer medicine for breast cancer.

"It's really important to understand the genetic defects a tumor cell has before we treat it," said lead author Guillermina Lozano, Ph.D., professor and chair of the Department of Genetics. "What we learned here is the complete opposite of what we expected. We thought tumors would respond better to treatment if the p53 gene were normal. But the opposite was true, and for a really interesting reason."

Lozano said the research in mouse models showed that non-mutated p53 halted cell division, initiating a senescence (cell aging) process that allowed cells to survive. These senescent cells produce factors that stimulate adjacent cells to grow, fueling the relapse. Mutant p53 cells do not arrest and proceed through the cell cycle into cell division with broken chromosomes caused by the chemotherapy.

"That's a signal for the cell to die," she said. "It can't go any farther."

P53 status crucial to predicting response

The tumor suppressor p53 is mutated or inactivated in the majority of cancers, and about one-third of breast cancers have mutations in the gene. It has long been thought that normal p53 results in a better chemotherapy response, but the evidence in breast cancer has been conflicting.

According to the National Cancer Institute, about 227,000 women in the United States are diagnosed with breast cancer each year.

In this study, doxorubicin-treated p53 mutant tumor cells did not stop cell proliferation, leading to abnormal mitoses and cell death, whereas tumors with normal p53 arrested, avoiding mitotic catastrophe.

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Preclinical Research Shows Normal Gene Hinders Breast Cancer Chemotherapy

OMAHA, Neb.--(BUSINESS WIRE)--

Transgenomic, Inc. (TBIO) announced that the US Patent and Trademark Office has issued patent number US 8,137,919 entitled Method of Determining the Sensitivity of Cancer Cells to EGFR Inhibitors including Cetuximab, Panitumumab and Erlotinib. The patent was exclusively licensed to Transgenomic by the Montefiore Medical Center (Bronx, NY, US) and includes all tumor types and targeted therapies that may be influenced by PIK3CA mutation status.

Montefiore inventors Drs. Sanjay Goel and John Mariadason have demonstrated that key mutations in the gene PIK3CA are powerful predictors for the efficacy of EGFR-targeted therapies such as cetuximab (Erbitux), panitumumab (Vectibix) and erlotinib (Tarceva). These findings were published in the June 2012 issue of Clinical Colorectal Cancer by the same researchers and have been reproduced in other independent studies.

Assays using Transgenomics proprietary SURVEYOR Scan, REVEAL ICE COLD-PCR and BLOCker-Sequencing for complete detection of PIK3CA mutations have been developed. The extremely high sensitivity of Transgenomics REVEAL ICE COLD-PCR technology enables the use of virtually any sample type including blood and circulating tumor cells. Non-invasive testing allows for more frequent and accurate profiling of a cancer as it responds to treatment and gains additional mutations.

The recent issuing of this important patent is a significant milestone in the continued development of our genetic biomarker intellectual property portfolio, said Craig Tuttle, CEO of Transgenomic. Since exclusively licensing this patent we have been able to effectively apply our high sensitivity mutation detection technologies, such as SURVEYOR Scan, REVEAL ICE COLD-PCR and BLOCker-sequencing, to PIK3CA assays in order to be able to detect genetic variations in very low mutant load samples, such as plasma, serum and circulating tumor cells.

Tuttle added that, The number of genes associated with the effectiveness of targeted cancer treatments is increasing; our strategy is to provide a complete portfolio of best-in-class kits for clinically relevant mutations using our proprietary and extremely sensitive technologies. These assays will also be available through our CLIA and Pharmacogenomics laboratories to support clinicians and pharmaceutical research and trials.

About Transgenomic

Transgenomic, Inc. (www.transgenomic.com) is a global biotechnology company advancing personalized medicine in cancer and inherited diseases through its proprietary molecular technologies and world-class clinical and research services. The Company has three complementary business divisions: Transgenomic Pharmacogenomic Services is a contract research laboratory that specializes in supporting all phases of pre-clinical and clinical trials for oncology drugs in development. Transgenomic Clinical Laboratories specializes in molecular diagnostics for cardiology, neurology, mitochondrial disorders, and oncology. Transgenomic Diagnostic Tools produces equipment, reagents, and other consumables that empower clinical and research applications in molecular testing and cytogenetics. Transgenomic believes there is significant opportunity for continued growth across all three businesses by leveraging their synergistic capabilities, technologies, and expertise. The Company actively develops and acquires new technology and other intellectual property that strengthen its leadership in personalized medicine.

Forward-Looking Statements

Certain statements in this press release constitute forward-looking statements of Transgenomic within the meaning of the Private Securities Litigation Reform Act of 1995, which involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Forward-looking statements include, but are not limited to, those with respect to management's current views and estimates of future economic circumstances, industry conditions, company performance and financial results, including the ability of the Company to grow its involvement in the diagnostic products and services markets. The known risks, uncertainties and other factors affecting these forward-looking statements are described from time to time in Transgenomic's filings with the Securities and Exchange Commission. Any change in such factors, risks and uncertainties may cause the actual results, events and performance to differ materially from those referred to in such statements. Accordingly, the Company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 with respect to all statements contained in this press release. All information in this press release is as of the date of the release and Transgenomic does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

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PIK3CA Gene Patent for Predicting Response to Targeted Therapy Issued – Exclusively Licensed to Transgenomic

A MAJOR scientific breakthrough has enabled the mapping of an unborn baby's entire genetic code using DNA taken from its parents.

Scientists at Seattle's University of Washington said their new technique could make it possible to scan for 3500 genetic disorders before birth, ABC News reported today.

The amniocentesis procedure currently used to diagnose disorders in babies - including Down's Syndrome, spina bifida, cystic fibrosis and muscular dystrophy - is invasive for the mother and can cause a miscarriage.

In the groundbreaking new research, scientists harnessed tiny traces of a baby's free-floating DNA, found in the 18-week pregnant mother's blood. They then tested DNA from her blood sample and DNA from the father's saliva.

By using these pieces of the genetic jigsaw puzzle, researchers were able to reconstruct the entire genetic code of the unborn baby boy. They were then able to see what spontaneous genetic mutations had arisen.

Scientists conceded that the breakthrough raised "many ethical questions" because early detection of disorders in babies could be used as a basis for abortion, an issue that was immediately raised by pro-life campaigners, The (London) Daily Telegraph reported.

"This is an incredible breakthrough with huge ethical implications," Art Caplan, a professor of medical ethics at University of Pennsylvania Medical Center, told ABC News.

Published in the Science Translational Medicine journal, the study was able to identify 39 of 44 "de novo", or new, genetic mutations before the baby was born. De novo mutations are not inherited from the parents and are responsible for a large percentage of genetic disorders. They are also thought to play a role in conditions like autism and schizophrenia.

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Baby in womb's entire gene code mapped

ScienceDaily (June 7, 2012) A team of UC Davis investigators has found that a genetic mutation may play an important role in the development of prostate cancer. The mutation of the so-called p53 (or Tp53) gene was previously implicated in late disease progression, but until now has never been shown to act as an initiating factor. The findings may open new avenues for diagnosing and treating the disease.

The study was published online in the journal Disease Models & Mechanisms and will appear in the November 2012 print edition in an article titled, "Initiation of prostate cancer in mice by Tp53R270H: Evidence for an alternate molecular progression."

"Our team found a molecular pathway to prostate cancer that differs from the current conventional wisdom of how the disease develops," said Alexander Borowsky, associate professor of pathology and laboratory medicine and principal investigator of the study. "With this new understanding, research can go in new directions to possibly develop new diagnostics and refine therapy."

Prostate cancer is the leading cancer diagnosis in men in the United States. Although it is curable in about 80 percent of men with localized disease, the rate is much lower if the cancer is highly virulent and has spread beyond the prostate gland.

The investigators developed a mouse model genetically engineered to have a mutation in the "tumor suppressor" gene, p53, specifically in the cells of the prostate gland. These mice were significantly more likely to develop prostate cancer than control mice without the mutation, and provided the first indication that the p53 mutation could be involved in the initiation of prostate cancer. They also note that the mutation of p53 in the prostate differs from loss or "knock-out" of the gene, which suggests that the mechanism is more complicated than simply a "loss of tumor suppression" and appears to involve an actively oncogenic function of the mutant gene.

The p53 gene encodes for a protein that normally acts as a tumor suppressor, preventing the replication of cells that have suffered DNA damage. Mutation of the gene, which can occur through chemicals, radiation or viruses, causes cells to undergo uncontrolled cell division. The p53 mutation has been implicated in the initiation of other malignancies, including breast, lung and esophageal cancers.

Other studies have associated p53 mutation with disease progression in prostate cancer, but this is the first to find that it can have a role in the early initiation of prostate cancer, as well.

Until now, understanding of the role of p53 was that mutation occurred exclusively as a late event in the course of prostate cancer. Based on the findings in the new mouse model that the researchers developed, p53 mutation not only can initiate prostate cancer but might also be associated with early progression toward more aggressive forms of the disease.

Genetic mutations can initiate cancers in a variety of ways. Those include promotion of uncontrolled cell growth and loss of the gene's normal cell growth-suppressor functions. Exactly how the p53 mutation promotes the initiation and progression of prostate cancer remains to be clarified and is a focus of current research by the UC Davis team. They also are trying to gain an understanding of how the p53 mutation affects the effectiveness of standard treatments for prostate cancer, such as radiation and hormone therapy.

Another application of the discovery could be the development of a new diagnostic test for prostate cancer based on the presence of the p53 mutation as a biomarker.

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New role for p53 genetic mutation -- initiation of prostate cancer

Editor's Choice Main Category: Pregnancy / Obstetrics Also Included In: Genetics;Pediatrics / Children's Health Article Date: 08 Jun 2012 - 12:00 PDT

Current ratings for: 'Genetic Screening During Pregnancy Shows Promise'

1 (1 votes)

The researchers findings open up the possibility of assessing a fetus non-invasively for all single-gene disorders.

Approximately 1% of newborns are born with disorders that are caused by a defect in a single gene. These "Mendelian" disorders include cystic fibrosis, Huntington's disease, and Tay-Sachs disease.

In the future, the new non-invasive technique could help screen for these types of genetic mutations in the fetus without increasing the risk of miscarriage, said Jay Shendure and his team at the University of Washington.

Shendure explained: "This work opens up the possibility that we will be able to scan the whole genome of the fetus for more than 3,000 single-gene disorders through a single, non-invasive test."

At 18.5 weeks gestation, the researchers were able to map the whole genome of a fetus and then reconstructed it using DNA from the mother's blood plasma and saliva from the father.

Although fetal DNA is found in the mother's blood plasma, it can be challenging to distinguish which genetic signature belongs to the fetus and which belongs to the mother. As a result the team used a new technique in order to identify blocks of haplotypes (genetic variation), that could be traced back to the mother's genome.

The researchers were then able to use this information, together with data from the father's saliva sample, to determine which genomes the fetus inherited. The team then conducted a more intensive examination of the mother's DNA sample in order to identify new genetic variations that appeared only in the fetal genome.

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Genetic Screening During Pregnancy Shows Promise

At the American Society for Clinical Oncology meeting in Chicago this week, oncologists gathered at a panel on gene patenting to learn more about the subject and how it might affect their work. Session chair Kenneth Offit of the Memorial Sloan-Kettering Cancer Center asked the audience how many thought gene patenting should be stopped, and nearly everyone in the room raised their hands.

On the anti-patenting side was Roger Klein of the Bloodcenter of Wisconsin. Klein, who is also a party to the Myriad BRCA patent case, discussed both the Myriad case and the case of Mayo v. Prometheus, which was recently decided by the US Supreme Court. The verdict in that case which went against Prometheus and its patent on a method for finding the right dosage of thiopurine to give a patient was an important step in clarifying and limiting the patentability of medical relationships, Klein said. This may seem like a far-away issue to most doctors, he added, but with personalized medicine becoming a reality, doctors are going to be using genomic and genetic variants to treat patients in a number of ways sometimes multiple variants and genes at the same time and "it's untenable to have the individual genes and variants patented."

"We cannot have encumbrances like patents," he added. "It's obstructing our ability to gather clinical data and track our patients. We all know that gene patients prevent us from doing things we should and could do to benefit our patients."

On the pro-patenting side was the Biotechnology Industry Organization's Hans Sauer, who said that there are more sides to gene patenting than just human genes. Although the Myriad case and Prometheus to a lesser extent have gained a lot of notoriety, Sauer said what is forgotten is that most gene patents are taken out on plant genes or pathogen genes that companies are using to create better ways to grow crops or develop anti-pathogenic agents. "If the ACLU is at fault for anything, it's not caring about the consequences of this fight to so many other companies," Sauer added. "These things are important and they're not often discussed in this context." He also said that patenting a gene doesn't mean a company owns it, or owns pieces of people; all it means is that they have exclusive rights to sell a product or make a product based on it for a short period of time. And, he added, it's not just about genes. If a company is not allowed to patent isolated bits of DNA, will dyes from plants, or bacteria-based biofuels, or medicinal substances be next, he asked.

At the end of the session, Offit once again asked the audience whether they believe gene patenting to be wrong. About half of those who had previously said yes conceded that they'd be willing to think about the issue.

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ASCO: The Two Sides of Gene Patenting

His new book's title might suggest otherwise. But Lee Gutkind, co-author of An Immense New Power to Heal: The Promise of Personalized Medicine, remains only "cautiously optimistic" about how the sequencing of the human genome can improve health care.

Gutkind is the Pittsburgh native and veteran nonfiction author of works including Many Sleepless Nights, about organ transplantation. The new book, which Gutkind co-wrote with Pagan Kennedy, uses stories of doctors and patients to map the state of the art. But it begins by recalling the fanfare surrounding President Clinton's 2000 announcement of that historic sequencing. That the breakthrough would revolutionize medicine seemed inevitable.

Indeed, genomic medicine which is encompassed by the broader term "personalized medicine" has already produced treatments including the breast-cancer drug Herceptin. And there are gene-based diagnostic tests, like Oncotype DX (which predicts whether chemotherapy will work on a particular breast tumor).

Meanwhile, the idea of medicine made not for everyone, but for particular patients, has even inspired UPMC to announce plans for a $300 million Center for Innovative Science, with a focus on personalized medicine.

But Clinton's speech that day in 2000 which provides the new book's title foretold a bullishness on genomic medicine that Gutkind considers premature. As Gutkind characterized such expectations in a recent phone interview, "We'll figure out what genes cause what diseases, and deal with the genes: We'll annihilate them or we'll plan in advance if you have the cancer gene, we'll figure out how to get rid of the cancer gene."

But such expectations are "something greater than could possibly be achieved," says Gutkind.

"For one thing, there are very, very few genes, a single gene, that leads to a single disease," he says. "Very often [it's] a combination of 12, 30, 40 or a hundred different genes that get you there." So knowing how one gene works, by itself, often is medically insufficient.

Moreover, while the amount of new information gene-sequencing has created is indisputably vast, knowing what that information means is a different matter. As Gutkind notes, "We haven't even catalogued the information." And there is also much more to learn about how genes behave in the presence of both environmental influences (pollution, say) and human behavior (like diet and exercise).

All in all, says Gutkind, the genomic revolution "may be a miracle, but it's a miracle that it's going to take half a century to make."

Yet there are aspects of personalized medicine that can make a difference today, says Gutkind, who now splits his time between Arizona (where he teaches) and Pittsburgh (where he runs the Creative Nonfiction Foundation, whose In Fact Books imprint published Immense New Power). They're just not the aspects that get the most attention.

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The author of a new book says don't expect gene-based therapies to save your bacon just yet.

CARLSBAD, Calif., June 5, 2012 /PRNewswire/ -- Life Technologies Corporation (NASDAQ: LIFE) today announced an expanded Ion AmpliSeq product line with the launch of new breakthrough Comprehensive Cancer and Inherited Disease Panels. These first of kind panels, when coupled with Ion AmpliSeq Designer V1.2, Ion AmpliSeq Library Kit 2.0 and the new Ion Reporter Software, represent complete solutions for scientists researching the genetic basis of human diseases.

Sequencing the millions of cancer research samples stored in bio-repositories around the world is a primary unmet need of the cancer research community. Analyzing these samples using next generation sequencing (NGS) has been difficult, as typically only nanogram amounts of DNA can be isolated, far less than current commercial protocols require. In addition, NGS creates a flood of data, requiring expensive bioinformatics expertise to interpret. The latest set of Ion AmpliSeq and Ion Reporter products from Ion Torrent offer turn-key solutions to overcome these challenges.

Bringing Simplicity and Speed to Disease Research Workflows

Ion AmpliSeq Panels, whether predesigned and therefore ready-to-use, or custom built to probe specific genes of interest, deliver a simplified, single day workflow comprising target selection, amplification, sequencing and analysis. Further, when using Ion Reporter Software, the integrated workflow also includes annotated readout detailing the biological significance of observed gene mutations. The breakthrough Ion AmpliSeq technology requires only tens of nanograms of input DNA, compared to technologies offered by other companies that require hundreds of nanograms or even micrograms of starting material.Orthogonal confirmation of variants observed with Ion AmpliSeq Panels is readily accomplished by selecting from 4.5 million ready-to-use TaqMan SNP Genotyping assays or by designing a custom TaqMan assay. TaqMan assays deliver "gold standard" sensitivity and specificity for SNP genotyping, and they may be analyzed in standard or digital PCR mode if increased sensitivity is required to detect low frequency or somatic mutations.

Scalability Demonstrated With Latest Edition of Ion AmpliSeq Designer Software

Initially launched in March, Ion AmpliSeq Designer has been immediately adopted by researchers world-wide, with over 1,000 custom designs submitted since inception. Ion AmpliSeq Designer Version 1.2 provides an additional leap in performance by generating up to 3,072 amplicons in a single tube allowing capture of up to 1 Mb of genetic sequence. This high level of multiplexing streamlines the workflow by ensuring that only 1 or 2 primer pools are needed for custom designs and also reduces the amount of input DNA required for analysis. Ion AmpliSeq Designer delivers exceptional performance, with target design rates and coverage uniformity up to 98%.

Improved Performance of Ion AmpliSeq Cancer Panel

In October of 2011 Ion Torrent launched the Ion AmpliSeq Cancer Panel, which has quickly become the product of choice for scientists working to advance clinical cancer research. Now, by pairing this 46 gene cancer hot spot panel with the new Ion AmpliSeq Library Kit 2.0, scientists can detect rare somatic mutations and enjoy 98% coverage uniformity and further reductions in strand bias.

New Ion AmpliSeq Comprehensive Cancer Panel

With input from leading cancer research institutions, the Ion AmpliSeq Comprehensive Cancer Panel (CCP) reveals tumor mutation profiles and is optimized for use with formalin fixed paraffin embedded, (FFPE) tissues. This panel allows sensitive, high coverage detection of rare genetic variants by employing more than 16,000 primer pairs targeting over 400 genes involved in tumor formation. Compared to whole exome sequencing, Ion AmpliSeq CCP requires only 40 ng of input DNA, has a significantly lower price, and provides nearly 10-fold better coverage of individual genes, providing better sensitivity and specificity to detect somatic mutations.The Ion AmpliSeq Comprehensive Cancer Panel delivers exceptional quality, with coverage uniformity and on target bases both greater than 90%.

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New Breakthrough Ion AmpliSeq™ Technology Delivers the Most Rapid and Comprehensive Sequencing of Gene Mutations to ...

DEERFIELD, Ill.--(BUSINESS WIRE)--

Baxter International Inc. (BAX) today announced that it has entered into an exclusive global agreement with Chatham Therapeutics, LLC, an affiliate of Asklepios BioPharmaceutical, Inc. (AskBio), for the development and commercialization of potential treatments for hemophilia B utilizing Chathams gene therapy technology.

The collaboration will allow Baxter to investigate Chathams Biological Nano ParticlesTM (BNP), an advanced recombinant adeno-associated virus-(rAAV) based gene therapy technology that has shown potential therapeutic benefit in early clinical studies. A small independent study involving six patients using Chatham technology components was the topic of a 2011 article in The New England Journal of Medicine.i This agreement will involve the next generation of this gene therapy technology, which Baxter and Chatham will investigate through U.S.-based hemophilia B clinical trials. Baxter has obtained global rights for the marketing and commercialization of the new treatment.

''This collaboration demonstrates Baxters ongoing commitment to scientific innovation in advancing treatment options for patients living with hemophilia. This initiative complements Baxters extensive hemophilia portfolio and helps to address unmet needs of hemophilia patients,'' said Ludwig Hantson, Ph.D., president of Baxters BioScience business.

Baxter made a $25 million upfront cash payment for the development and advancement of the program through early clinical trials, and will record this amount as a special pre-tax in-process research and development charge in the second quarter of 2012. Baxter may make additional payments over the next several years based on certain development and commercial milestones.

''This agreement initiates a clinical development collaboration dedicated to advancing a potential long-term treatment paradigm for hemophilia patients. We look forward to working with Baxter and view this transaction as the optimal path toward providing a sustainable therapeutic to a worldwide patient population,'' said Jade Samulski, Vice President at AskBio and Co-Founder of Chatham Therapeutics.

Hemophilia B is the second most common typeof hemophilia (also known as Christmas disease) and is the result of insufficient amounts of clotting factor IX, a naturally occurring protein in blood that controls bleeding.ii Hemophilia B occurs in about one in 25,000 males, with approximately 4,000 people in the United States currently diagnosed with the disease.iii Hemophilia B is often a debilitating, chronic disease with complications that include bleeding episodes, hemophilic arthropathy (bleeding into a joint) and hospitalization.iv

Baxter is pursuing a number of research opportunities in hemophilia. The company is conducting a Phase I/III clinical trial of BAX326, a recombinant Factor IX being evaluated for the treatment of patients with hemophilia B, and expects to file for U.S. approval by the end of 2012.

About Baxter International Inc.

Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

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Baxter Announces Collaboration with Chatham Therapeutics for Factor IX Hemophilia B Gene Therapy Treatment

OMAHA, Neb.--(BUSINESS WIRE)--

Transgenomic, Inc. (TBIO) today announced the commercial launch of its ICE COLD-PCR mutation detection technology, a breakthrough technology enabling unmatched sensitivity and complete DNA mutation detection using the standard sequencing equipment already installed in laboratories around the world. The launch coincides with the 2012 annual meeting of the American Society of Clinical Oncology.

ICE COLD-PCR is capable of identifying mutation frequencies as low or lower than 0.01% which surpasses the limits of currently available mutation detection tests. This extremely high sensitivity enables detection of mutations from virtually any sample type including tissue biopsies, blood, and circulating tumor cells (CTCs). Mutation profiling from blood and CTCs may benefit cancer patients because it avoids the risks of additional surgical procedures while providing an up-to-date picture of any additional mutations the cancer may have acquired throughout treatment.

An ICE COLD-PCR kit for enrichment of KRAS mutations is now available worldwide to molecular diagnostic laboratories for use with standard DNA sequencing equipment. Transgenomic plans to expand the ICE COLD-PCR testing platform to include other therapeutically relevant mutations including BRAF, EGFR, and PIK3CA.

The broad use of ICE COLD-PCR has the potential to revolutionize cancer screening, diagnosis, monitoring, and therapy selection said Craig Tuttle, Chief Executive Officer of Transgenomic. It offers us the ability to accurately perform safer, less invasive, and more frequent assessments of a cancer and its mutations, all through a simple blood draw. Ultimately, the goal is to provide real-time monitoring of cancer progression, resistance mutations and response to therapy. With the proliferation of targeted anti-cancer drugs now available or in clinical trials, ICE COLD-PCR will help determine the right path for each patient at every step of his or her treatment, making precision medicine even more precise.

Mr. Tuttle added: ICE COLD-PCR provides extreme sensitivity and coverage to ensure that mutations are not missed, both are needed for reliable mutation profiling from blood, CTCs, and small sample sizes. Because it is used with the sequencing equipment already installed in labs around the world, we expect broad and sustained adoption of this technology, with kit sales beginning this year. Each of the markets addressed by ICE COLD-PCR diagnosis, monitoring, and disease recurrence is substantial, providing a significant value-creation opportunity for Transgenomic.

ICE COLD-PCR technology was developed in collaboration with the Dana-Farber Cancer Institute and is supported by multiple validation studies confirming reproducible mutation detection at very high sensitivity up to 1,000 times more sensitive than traditional PCR techniques. The technology is also being evaluated in an ongoing study with The University of Texas MD Anderson Cancer Center to analyze DNA isolated from CTCs.

About Transgenomic, Inc.

Transgenomic, Inc. (www.transgenomic.com) is a global biotechnology company advancing personalized medicine in cancer and inherited diseases through its proprietary molecular technologies and world-class clinical and research services. The Company has three complementary business divisions: Transgenomic Pharmacogenomic Services is a contract research laboratory that specializes in supporting all phases of pre-clinical and clinical trials for oncology drugs in development, Transgenomic Clinical Laboratories, which specializes in molecular diagnostics for cardiology, neurology, mitochondrial disorders, and oncology, and Transgenomic Diagnostic Tools which produces equipment, reagents, and other consumables that empower clinical and research applications in molecular testing and cytogenetics. Transgenomic believes there is significant opportunity for continued growth across all three businesses by leveraging their synergistic capabilities, technologies, and expertise. The Company actively develops and acquires new technology and other intellectual property that strengthen its leadership in personalized medicine.

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Transgenomic Launches Breakthrough Blood-Based Cancer Gene Testing Technology at 2012 ASCO Annual Meeting

ScienceDaily (June 1, 2012) Type 2 diabetes is popularly associated with obesity and a sedentary lifestyle. However, just as there are obese people without type 2 diabetes, there are lean people with the disease.

It has long been hypothesised that type 2 diabetes in lean people is more 'genetically driven'. A new study from a research team led by the Peninsula College of Medicine and Dentistry (PCMD), University of Exeter, which involved research institutions from around the world, has for the first time proved that lean type 2 diabetes patients have a larger genetic disposition to the disease than their obese counterparts. The study has also identified a new genetic factor associated only with lean diabetes sufferers.

The study is published in PLoS Genetics.

Using genetic data from genome-wide association studies, the research team tested genetic markers across the genome in approximately 5,000 lean patients with type 2 diabetes, 13,000 obese patients with the disease and 75,000 healthy controls.

The team found differences in genetic enrichment between lean and obese cases, which support the hypothesis that lean diabetes sufferers have a greater genetic predisposition to the disease. This is in contrast to obese patients with type 2 diabetes, where factors other than type 2 diabetes genes are more likely to be responsible. In addition, genetic variants near the gene, LAMA1, were linked to type 2 diabetes risk for the first time, with an effect that appeared only in the lean patients.

Dr. John Perry, one of the lead authors of the study, said: "Whenever a new disease gene is found, there is always the potential for it to be used as a drug target for new therapies or as a biomarker, but more work is needed to see whether or not this new gene has that potential."

He added: "This is the first time that a type 2 diabetes gene has been found to act in this way -- we do not know why it should be associated in one sub-group of patients and not another. It could point to the fact that type 2 diabetes may not be one disease, but may represent a number of subgroups. Again, more work is required to prove this hypothesis."

Dr. Perry concluded: "This study is a truly international one, bringing together research teams from around the world and leading UK institutions such as the University of Oxford, the University of Cambridge, King's College London, the University of Dundee and the University of Edinburgh."

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'Jack Spratt' diabetes gene identified

ScienceDaily (May 31, 2012) When flies are made to lose a gene with links to Restless Legs Syndrome (RLS), they suffer the same sleep disturbances and restlessness that human patients do. The findings reported online on May 31 in Current Biology, a Cell Press publication, strongly suggest a genetic basis for RLS, a condition in which patients complain of an irresistible urge to move that gets worse as they try to rest.

"Although widely prevalent, RLS is a disorder whose pathophysiological basis remains very poorly understood," said Subhabrata Sanyal of Emory University School of Medicine. "The major significance of our study is to highlight the fact that there might be a genetic basis for RLS. Understanding the function of these genes also helps to understand and diagnose the disease and may offer more focused therapeutic options that are currently limited to very general approaches."

Sanyal's team recognized that a number of genome-wide association studies in humans had suggested connections between RLS and variation in a single gene (BTBD9).

"BTBD9 function or its relationship to RLS and sleep were a complete mystery," Sanyal said.

His team realized that there might be a way to shed some light on that mystery in fruit flies. Flies have a single, highly conserved version of the human BTBD9. They decided to test whether the gene that had turned up in those human studies would have any effect on sleep in the insects. In fact, flies need sleep just like humans do, and their sleep patterns are influenced by the same kinds of brain chemistry.

The researchers now report that flies lacking their version of the RLS-associated gene do lose sleep as they move more. When those flies were treated with a drug used for RLS, they showed improvements in their sleep.

The studies also yielded evidence about how the RLS gene works by controlling dopamine levels in the brain as well as iron balance in cells. Sanyal said his team will continue to explore other RLS-related genes that have been identified in human studies in search of more details of their interaction and function.

"Our results support the idea that genetic regulation of dopamine and iron metabolism constitute the core pathophysiology of at least some forms of RLS," the researchers write.

More broadly, they say, the study emphasizes the utility of simple animals such as fruit flies in unraveling the genetics of sleep and sleep disorders.

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Flies with restless legs syndrome point to a genetic cause

CAMBRIDGE, Mass. & CHICAGO--(BUSINESS WIRE)--

Foundation Medicine, Inc., a molecular information company that brings comprehensive cancer genomic analysis to routine clinical care, today announced results from two studies using next-generation sequencing (NGS) to provide actionable information about genomic tumor alterations in individual patients cancers across all solid tumor types. The studies, being presented this week in an oral and poster session at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), provide new evidence of the important role and clinical impact of NGS in cancer treatment.

These data follow Foundation Medicines recent launch of FoundationOne, the first pan-cancer, fully informative genomic profile for all solid tumors.

These studies, along with other results previously presented and published, provide unequivocal evidence of the significant clinical value of NGS-based comprehensive genomic analysis, said Michael J. Pellini, president and chief executive officer, Foundation Medicine. One test, using a very small amount of tissue, can enable physicians to tailor treatment to a patients molecular subtype. With our pan-cancer genomic profile now commercially available, physicians will have a critical decision-making tool to assist them in making the most appropriate therapeutic choices for their patients with cancer.

The first study, Discovery of Recurrent KIF5B-RET Fusions and Other Targetable Alterations from Clinical NSCLC Specimens (Abstract # 7510), was completed in collaboration with researchers at Dana-Farber Cancer Institute and assayed cancer-relevant genes in 24 cases of non-small cell lung cancer (NSCLC). Highlights of the analysis include:

Many non-small cell lung cancers have oncogenic alterations that may be sensitive to a targeted therapeutic approach, which can lead to better outcomes for individual patients, said Marzia Capelletti, Ph.D., Research Fellow in Medicine, Dana-Farber Cancer Institute. The challenge for physicians is to comprehensively understand the patients cancer by characterizing the genomic profile and develop a rational treatment strategy. The results of this study clearly demonstrate that there is a need to have a reliable tool to identify the particular molecular drivers of a tumor to help select appropriate therapies for individual patients.

An additional study, Next-Generation Sequencing Reliably Identifies Actionable Genomic Changes in Common and Rare Solid Tumors: The FMI Experience with the Initial 50 Consecutive Patients (Abstract #10590), utilized NGS to identify actionable genomic alterations across a variety of solid tumors in the first 304 clinical specimens (poster updated with clinical experience through May 1, 2012) analyzed by Foundation Medicines CLIA-approved laboratory. Alterations were defined as actionable if linked to an approved therapy in the tumor under study or another solid tumor; a known or suspected contraindication to a given therapy; or a clinical trial linked to the alteration. Lung, breast, colorectal, ovarian and pancreatic cancers were the most common solid tumors identified among 16 primary tumor types. In the analysis:

The complex nature of cancer and the transformation of cancer care, prompted by advanced understanding of genomic subtypes and emergence of targeted therapies, make the detection of alterations to guide therapeutic decision-making more critical than ever, said Gary Palmer, M.D., J.D., M.P.H., senior vice president of medical affairs and commercial development, Foundation Medicine, and lead author of the study. This NGS assay makes it possible for clinicians to make the best possible therapeutic choices, minimize the use of ineffective therapies and enhance enrollment in clinical trials appropriate for the individual patient.

Foundation Medicines first commercial offering, FoundationOne, is a fully informative genomic profile that allows any oncologist to use the same technology that informed the studies presented here as a clinical decision making tool in their own practice. FoundationOne uses routine, formalin-fixed, paraffin-embedded tumor samples. Test results are provided in a straightforward report that matches detected patients genomic alterations with potential treatment options and clinical trials.

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Foundation Medicine Announces New Data Using Next-Generation Sequencing to Detect Cancer-Related Mutations Not ...

Category: Science & Technology Posted: June 1, 2012 04:59AM Author: Guest_Jim_*

A future with a failing body is not something anyone looks forward to, so researchers are looking for ways to control the process. We already have medications and treatments so senior citizens can stay active with each passing year, but researchers are still working towards a way to stop or completely reverse the aging process itself.

Studies have discovered that as people age, the telomeres at the ends of their chromosomes fall off. Preventing this from happening inhibits aging, but can also cause cancer, which is an unchecked and uncontrolled mutation of normal cells. Researchers have known that inflammation is also connected to aging and cancer, but did not know how these three, seemingly unconnected, things were intertwined. Those at NYU Langone Medical Center / New York University School of Medicine have discovered that the link is through the AUF1 gene.

This gene controls inflammation by turning off that natural response before septic shock can occur. What the researchers discovered is that AUF1 also triggers the activation of telomerase, an enzyme that repairs telomeres, or kills cells by not activating, to repair the telomeres. This one gene regulates inflammation, can prevent accelerated aging, and prevent cancer by not activating telomerase. The researchers' next step is to examine the human population to see if mutations of the AUF1 gene are linked to different diseases.

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Inflammation, Aging and Cancer All Linked to One Gene

Newswise The same gene variations that make it difficult to stop smoking also increase the likelihood that heavy smokers will respond to nicotine-replacement therapy and drugs that thwart cravings, a new study shows.

The research, led by investigators at Washington University School of Medicine in St. Louis, will appear online May 30 in the American Journal of Psychiatry.

The study suggests it may one day be possible to predict which patients are most likely to benefit from drug treatments for nicotine addiction.

Smokers whose genetic makeup puts them at the greatest risk for heavy smoking, nicotine addiction and problems kicking the habit also appear to be the same people who respond most robustly to pharmacologic therapy for smoking cessation, says senior investigator Laura Jean Bierut, MD, professor of psychiatry. Our research suggests that a persons genetic makeup can help us better predict who is most likely to respond to drug therapy so we can make sure those individuals are treated with medication in addition to counseling or other interventions.

For the new study, the researchers analyzed data from more than 5,000 smokers who participated in community-based studies and more than 1,000 smokers in a clinical treatment study. The scientists focused on the relationship between their ability to quit smoking successfully and genetic variations that have been associated with risk for heavy smoking and nicotine dependence.

People with the high-risk genetic markers smoked an average of two years longer than those without these high-risk genes, and they were less likely to quit smoking without medication, says first author Li-Shiun Chen, MD, assistant professor of psychiatry at Washington University. The same gene variants can predict a persons response to smoking-cessation medication, and those with the high-risk genes are more likely to respond to the medication.

In the clinical treatment trial, individuals with the high-risk variants were three times more likely to respond to drug therapy, such as nicotine gum, nicotine patches, the antidepressant buproprion and other drugs used to help people quit.

Tobacco use is the leading cause of preventable illness and death in the United States and a major public health problem worldwide. Cigarette smoking contributes to the deaths of an estimated 443,000 Americans each year. Although lung cancer is the leading cause of smoking-related cancer death among both men and women, tobacco also contributes to other lung problems, many other cancers and heart attacks.

Bierut and Chen say that the gene variations they studied are not the only ones involved in whether a person smokes, becomes addicted to nicotine or has difficulty quitting. But they contend that because the same genes can predict both heavy smoking and enhanced response to drug treatment, the genetic variants are important to the addiction puzzle.

Its almost like we have a corner piece here, Bierut says. Its a key piece of the puzzle, and now we can build on it. Clearly these genes arent the entire story other genes play a role, and environmental factors also are important. But weve identified a group thats responding to pharmacologic treatment and a group thats not responding, and thats a key step in improving, and eventually tailoring, treatments to help people quit smoking.

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Genes Predict if Medication Can Help You Quit Smoking

Public release date: 31-May-2012 [ | E-mail | Share ]

Contact: Holly Korschun hkorsch@emory.edu 404-727-3990 Emory University

Scientists have discovered that mutations in the gene BTBD9, which is linked with restless legs syndrome (RLS) in humans, disturb sleep in fruit flies. The mutant flies wake up more often during sleep periods, which resembles a key feature of human RLS.

The same mutations in BTBD9 also reduce levels of the neurotransmitter dopamine in the flies. Some kind of deficiency in dopamine signaling is thought to lie behind RLS in humans.

The results are published in the journal Current Biology.

"Flies and humans are distant from each other on the evolutionary tree, yet the same gene seems to be regulating a fundamental process in both organisms and affecting how soundly they sleep," says senior author Subhabrata Sanyal, PhD, assistant professor of cell biology at Emory University School of Medicine.

People with RLS experience unpleasant sensations in their legs and urges to move them, interfering with the ability to sleep. Genetics plays a major role in RLS, and most people with RLS have a close family member with the disorder. A variant in the BTBD9 gene accounts for about half of the risk for RLS in the population, according to multiple genetic studies (http://1.usa.gov/LqrO5L).

While medications exist to treat RLS, in some patients they are ineffective or have side effects. Researchers don't have a good understanding of what is going wrong in the nervous system in people affected by RLS, or what the BTBD9 gene does. Studying the fly version of BTBD9 could shed light on the basic biology and eventually lead to improved treatments for humans.

Postdoctoral fellow Amanda Freeman, the first author of the paper, examined flies' sleep behavior by putting individual flies into tubes with infrared sensors, which can detect when a fly moves across the middle of the tube. If a fly doesn't cross the beam for five minutes, it's considered asleep. She found that the BTBD9 mutant flies woke up more often during the night.

Disabling BTBD9 also makes flies more mobile while awake. Mutant flies confined in a tube move back and forth more often, leading Freeman and Sanyal to dub the mutant flies "wanderlust."

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Restless legs syndrome in fruit flies: Mutation in fly version of a human RLS gene disturbs sleep