HPV Havoc

Human papillomavirus promotes genomic damage by inserting near host genes involved in cancer.

Feb 1, 2014
Tracy Vence

INVADERS: Human papillomavirus particles (shown in this artist’s rendering) can integrate into the human genome and cause chromosomal instability. © DAVID MACK/SCIENCE SOURCE

EDITOR'S CHOICE IN GENETICS & GENOMICS

The paper
K. Akagi et al., “Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability,” Genome Research, doi:10.1101/gr.164806.113, 2013.

The finding
Human papillomavirus (HPV) is known to promote mutations in its host’s DNA, though exactly how the virus contributes to genomic instability has been unclear. Researchers led by Maura Gillison of Ohio State University Comprehensive Cancer Center now show in human cancer cell lines and tumors that the sites where HPV integrates into the host genome are linked with genetic damage that may disrupt tumor suppressors and oncogenes.

The extent
“We [found] tremendous host genomic rearrangements happening immediately adjacent to the sites of the viral integration,” including deletions, amplifications, inversions, and even a case of chromosomal translocation, says coauthor David Symer, a geneticist at Ohio State. “It was remarkable to see the extent of the local genomic damage around the viral insertion sites.”

The damage
HPV plunked itself into the host genome at several points adjacent to genes involved in cancer development. In one case, the researchers found that integration of HPV deleted and rearranged portions of DIAPH2—a gene encoding a protein that plays a role in sister chromatid separation. Mutations in DIAPH2 are known to promote chromosomal instability, a hallmark of certain cancers.

The implications
The group has yet to show a direct, cancer-causing result of HPV’s mischievous insertions in the host genome. But variations in HPV integration sites and the resulting genomic damage could explain why the virus affects people differently, says Robert Ferris of the University of Pittsburgh Cancer Institute. “Everybody is exposed to HPV,” he says, “but only a subset of individuals contract HPV-associated cancers.”