Wei-Hua Shao,1 4,* Cheng-Yu Wang,4,5,* Lei-Yun Wang,1 4 Fan Xiao,1 4 De-Sheng Xiao,6 Hao Yang,4,5 Xue-Ying Long,7 Le Zhang,8 Heng-Gui Luo,9 Ji-Ye Yin,1 4 Wei Wu4,5
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Peoples Republic of China; 2Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Peoples Republic of China; 3Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, Peoples Republic of China; 4Department of Geratic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, Peoples Republic of China; 5National Clinical Research Center for Geriatric Disorders, Changsha, Hunan 410008, Peoples Republic of China; 6Department of Pathology, Xiangya Hospital/School of Basic Medicine, Central South University, Changsha 410078, Hunan, Peoples Republic of China; 7Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008, Peoples Republic of China; 8Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, Peoples Republic of China; 9Department of General Surgery, The Central Hospital of Xiangtan City, Xiangtan, Hunan, Peoples Republic of China
*These authors contributed equally to this work
Correspondence: Wei WuDepartment of Geratic Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, Peoples Republic of ChinaTel +86 731 89753053Email wwtw1972@126.com
Purpose: In order to clarify which variants of the MMR gene could provide current healthy members in affected families a more accurate risk assessment or predictive testing.Patients and Methods: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing.Results: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro.Conclusion: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.
Keywords: Lynch syndrome, genetic variation, mismatch repair gene, MSH2, chemotherapy resistance
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.
Read more:
A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in | CMAR - Dove Medical Press
- Main Show Only - Genetic Engineering - Coast to Coast AM - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- RTPB | Genetic Engineering [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Stop Monsanto From Poisoning Hawai'i: Genetic Engineering Chemical Warfare - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Informatics 161 PSA: Human Genetic Engineering - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Don't Trust Whole Foods or Other Health Food Stores For Non- GMO Foods | Genetic Engineering - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Genetic Engineering - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Easier Genetic Engineering! (Brainstorm Ep69) - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- TEDxUCIrvine - Francisco Ayala - Cloning, Genetic Engineering, [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Genetic Engineering in Agriculture - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Infowars Special Report : Genetic Engineering - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Glowing Rats and Extreme Genetic Engineering - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Endangered Cat Born at Audubon - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Danger of Genetic Engineering - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- AQA GCSE core science and B1 - Genetic Engineering - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- genetic engineering rDNA.wmv - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Genetic Engineering for Human Enhancement.mp4 - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Genetic Engineering - Seven Wonders of the Microbe World (6/7) - Video [Last Updated On: September 7th, 2012] [Originally Added On: September 7th, 2012]
- Promising new drug target for inflammatory lung diseases [Last Updated On: September 8th, 2012] [Originally Added On: September 8th, 2012]
- Mandatory GM Labeling Would Require Major Change [Last Updated On: September 10th, 2012] [Originally Added On: September 10th, 2012]
- GEN reports on ocular therapeutics targeting the retina [Last Updated On: September 11th, 2012] [Originally Added On: September 11th, 2012]
- Prop. 37: Another example of the perils of the initiative process [Last Updated On: September 15th, 2012] [Originally Added On: September 15th, 2012]
- Genetic test predicts risk for Autism [Last Updated On: September 19th, 2012] [Originally Added On: September 19th, 2012]
- Immediate withdrawal of unsafe GE corn vital - Greens [Last Updated On: September 20th, 2012] [Originally Added On: September 20th, 2012]
- Immediate withdrawal of unsafe GE corn vital [Last Updated On: September 20th, 2012] [Originally Added On: September 20th, 2012]
- NZ out of step on GE [Last Updated On: September 21st, 2012] [Originally Added On: September 21st, 2012]
- Ballot Watch: Labeling genetically engineered foods [Last Updated On: September 30th, 2012] [Originally Added On: September 30th, 2012]
- Just another GE mirage [Last Updated On: October 2nd, 2012] [Originally Added On: October 2nd, 2012]
- The GM Barnyard [Last Updated On: October 3rd, 2012] [Originally Added On: October 3rd, 2012]
- Free Engine [Last Updated On: October 3rd, 2012] [Originally Added On: October 3rd, 2012]
- Cellectis Publishes Results Paving the Way for New Therapeutic Approaches against Cancer and Genetic Diseases [Last Updated On: October 3rd, 2012] [Originally Added On: October 3rd, 2012]
- Does moral decision-making in video games mirror the real world? [Last Updated On: October 3rd, 2012] [Originally Added On: October 3rd, 2012]
- Animals engineered with pinpoint accuracy [Last Updated On: October 3rd, 2012] [Originally Added On: October 3rd, 2012]
- Valley farmers fear 'modified' wording in Prop. 37 [Last Updated On: October 4th, 2012] [Originally Added On: October 4th, 2012]
- No on Proposition 37 [Last Updated On: October 4th, 2012] [Originally Added On: October 4th, 2012]
- The Dangers of Genetic Engineering [Last Updated On: October 5th, 2012] [Originally Added On: October 5th, 2012]
- Are inhaled medications effective and safe in critically ill patients on mechanical ventilation? [Last Updated On: October 5th, 2012] [Originally Added On: October 5th, 2012]
- Calif. initiative will test appetite for GMO food [Last Updated On: October 7th, 2012] [Originally Added On: October 7th, 2012]
- Calif. initiative will test appetite for GMO food - Sat, 06 Oct 2012 PST [Last Updated On: October 7th, 2012] [Originally Added On: October 7th, 2012]
- California to vote on 'genetically modified' labels [Last Updated On: October 7th, 2012] [Originally Added On: October 7th, 2012]
- California initiative will test appetite for genetically modified foods [Last Updated On: October 7th, 2012] [Originally Added On: October 7th, 2012]
- Do we have an appetite for genetically modified food? [Last Updated On: October 7th, 2012] [Originally Added On: October 7th, 2012]
- Genetic labelling mooted in California [Last Updated On: October 7th, 2012] [Originally Added On: October 7th, 2012]
- California initiative to test appetite for 'genetically engineered' food [Last Updated On: October 7th, 2012] [Originally Added On: October 7th, 2012]
- New tool for making genetic engineering of microbial circuits reliably predictable [Last Updated On: October 10th, 2012] [Originally Added On: October 10th, 2012]
- Researchers develop new tool for making genetic engineering of microbial circuits reliably predictable [Last Updated On: October 10th, 2012] [Originally Added On: October 10th, 2012]
- A Welcome Predictability [Last Updated On: October 10th, 2012] [Originally Added On: October 10th, 2012]
- Engineered flies spill secret of seizures [Last Updated On: October 12th, 2012] [Originally Added On: October 12th, 2012]
- Genetic 'remix' key to evolution of bee behavior, researchers find [Last Updated On: October 15th, 2012] [Originally Added On: October 15th, 2012]
- Can vaccines be delivered via the lungs instead of by injection? [Last Updated On: October 15th, 2012] [Originally Added On: October 15th, 2012]
- Food labeling regulations [Last Updated On: October 16th, 2012] [Originally Added On: October 16th, 2012]
- Research and Markets: Therapeutic Antibody Engineering: Current and Future Advances Driving the Strongest Growth Area ... [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- Is there a difference between GE & GMO? [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- Port Townsend Food Coop: A Sad Story of GMO Crop Cross Pollination - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- PUT IT IN YOUR MOUTH! Yes to Prop 37 — it's your right to know what's in your food! - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- editta braun company: planet LUVOS (clip, 4:30) - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- Mimic: The Director's Cut (Blu-ray Trailer) - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- South Park Season 1 Episode 7 - An Elephant Makes Love to a Pig - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- Yes on Prop 37: Animated Video - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- The Day of the Triffids Part 1 Full Movie - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- YES on prop 37 "flashmob" march - Santa Cruz, CA Sept. 2012 - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- World's Weirdest Places Discussed - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- THE CLUB OF ROME - DEPOPULATION AGENDA 21 - THE UNHIVED MIND - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- 27-Medical BiotechnologySG Part II.Gene Therapy, Tissue Engineering and Nanotechnology.mov - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- 26-Medical BiotechnologySG Part Ic. Animal and Human Cloning and Genetic Engineering.mov - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- How to Clone Animals - Video [Last Updated On: November 2nd, 2012] [Originally Added On: November 2nd, 2012]
- Fringe Opening sequence (Season 3 - The Day We Died) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (Season 3 - Olivia) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (Season 3 - Entrada) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (Season 4) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (Season 3) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (Season 2) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (1985) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Dendritic Cells: Biology And Clinical Applications - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Port Townsend Food Coop: "I want my food untainted by GMOs" - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Catholic Priest vs. Biologist - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Watch Real Life Superhero Muscles Like Marvel's The Avengers - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (Season 1) - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Fringe Opening sequence (The Final Season: "Fight For The Future") - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- Port Townsend Food Coop: I Want To Know If GMOs Are In My Food - Video [Last Updated On: November 4th, 2012] [Originally Added On: November 4th, 2012]
- ProCognia jumps on expanded biosimilar collaboration [Last Updated On: November 7th, 2012] [Originally Added On: November 7th, 2012]