Featured Research

from universities, journals, and other organizations

HPV can damage genes, chromosomes directly by inserting own DNA into human DNA

Date:
November 7, 2013
Source:
Ohio State University Wexner Medical Center
Summary:
A study has identified a new mechanism by which the human papillomavirus (HPV) may contribute to cancer development. Using whole-genome sequencing, researchers show that strains of HPV that cause cervical, head and neck and other cancers can directly damage genes and chromosomes where they insert their DNA into human DNA.

"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. The virus does this by inserting its DNA into human DNA.
Credit: krishnacreations / Fotolia

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.

The two cancer-causing proteins, E6 and E7, silence two key tumor-suppressor genes in host cells, contributing to cancer development. "E6 and E7 are critically important for the virus to cause cancer. Our findings shed light on how HPV, and perhaps other viruses, can disrupt the structure of host chromosomes and genes and thereby contribute to cancer development," Gillison explains.

For this study, Symer, Gillison and their colleagues examined 10 cancer-cell lines and two head and neck tumor samples from patients. Along with whole-genome sequencing, the scientists used several molecular assays, including RNA sequencing, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH).

Key technical findings included:

  • The genome-wide analysis, at single nucleotide resolution, identified a striking and recurrent association between HPV integrants and adjacent genomic amplifications, deletions and translocations;
  • The HPV integrants mapped broadly across the human genome, with no evidence of recurrent integration into particular chromosomal hotspots;
  • The researchers proposed a "looping" model by which abnormal viral replication results in the extraordinary damage that occurs to host chromosomes at the sites of viral DNA insertion.

"Our study reveals new and interesting information about what happens to HPV in the 'end game' in cancers," Symer says. "Overall, our results shed new light on the potentially critical, catastrophic steps in the progression from initial viral infection to development of an HPV-associated cancer."


Story Source:

The above story is based on materials provided by Ohio State University Wexner Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. K. Akagi, J. Li, T. R. Broutian, H. Padilla-Nash, W. Xiao, B. Jiang, J. W. Rocco, T. N. Teknos, B. Kumar, D. Wangsa, D. He, T. Ried, D. E. Symer, M. L. Gillison. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Research, 2013; DOI: 10.1101/gr.164806.113

Cite This Page:

Ohio State University Wexner Medical Center. "HPV can damage genes, chromosomes directly by inserting own DNA into human DNA." ScienceDaily. ScienceDaily, 7 November 2013. <www.sciencedaily.com/releases/2013/11/131107132825.htm>.
Ohio State University Wexner Medical Center. (2013, November 7). HPV can damage genes, chromosomes directly by inserting own DNA into human DNA. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2013/11/131107132825.htm
Ohio State University Wexner Medical Center. "HPV can damage genes, chromosomes directly by inserting own DNA into human DNA." ScienceDaily. www.sciencedaily.com/releases/2013/11/131107132825.htm (accessed April 16, 2014).

Share This



More Health & Medicine News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins