HPV can damage genes and chromosomes directly, whole-genome sequencing study shows

PUBLIC RELEASE DATE:

7-Nov-2013

Contact: Darrell E. Ward Darrell.Ward@osumc.edu 614-293-3737 Ohio State University Wexner Medical Center

COLUMBUS, Ohio The virus that causes cervical, head and neck, anal and other cancers can damage chromosomes and genes where it inserts its DNA into human DNA, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James).

It's long been known that cancer-causing types of human papillomavirus (HPV) produce two viral proteins, called E6 and E7, which are essential for the development of cancer. However, they are not sufficient to cause cancer. Additional alterations in host-cell genes are necessary for cancer to develop. Here, scientists identified a new mechanism by which HPV may damage host DNA directly and contribute to cancer development.

Published in the journal Genome Research, this laboratory study used whole-genome sequencing to investigate the relationship between the HPV and host genomes in human cancers.

"Our sequencing data showed in vivid detail that HPV can damage host-cell genes and chromosomes at sites of viral insertion," says co-senior author David Symer, MD, PhD, assistant professor of molecular virology, immunology and medical genetics at the OSUCCC James.

"HPV can act like a tornado hitting the genome, disrupting and rearranging nearby host-cell genes," Symer explains. "This can lead to overexpression of cancer-causing genes in some cases, or it can disrupt protective tumor-suppressor genes in others. Both kinds of damage likely promote the development of cancer."

"We observed fragments of the host-cell genome to be removed, rearranged or increased in number at sites of HPV insertion into the genome," says co-senior author Maura Gillison, MD, PhD, professor of medicine, epidemiology and otolaryngology and the Jeg Coughlin Chair of Cancer Research at the OSUCCC James. "These remarkable changes in host genes were accompanied by increases in the number of HPV copies in the host cell, thereby also increasing the expression of viral E6 and E7, the cancer-promoting genes."

HPV causes about 610,000 cancers annually worldwide, including virtually all cervical cancers, and many anogenital and head and neck cancers. How it causes cancer isn't completely understood.

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HPV can damage genes and chromosomes directly, whole-genome sequencing study shows