The potential link between an infection with DNA viruses and cancer has been well established in a number of cancer types. Over the past few decades, a better understanding cancer pathogenesis as novel aspects of DNA virus biology and the various mechanism involved including, for example, mutagenic integration into the host genomeand expression of oncogenic viral proteins, has played a key role in developing a defense against a number of cancers.

Based on the this understanding, the eradication of viral infections through prevention and vaccination programs and initiatives has had a drasticepidemiologicalimpact on the incidence of virus-associated cancers. An example of success was the discovery that most cervical cancers are caused by the sexually transmitted infection with human papillomavirus (HPV) and how widespread HPV immunization has reduced the impact of cervical cancer worldwide.

As a direct result of this success,researchers around the world have been working very hard to find even more associations, in part because viruses could provide more targets for vaccines to prevent or cure cancers.


This study highlights the importance of bioinformatics in defining the landscape of virus integration across cancer subtypes.

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However, the results of this large-scale analysis of the association between DNA viruses and human malignancies suggest that many of the most common cancers are not associated with DNA viruses. The findings of the study are published in the August 2013 issue of theJournal of Virology, a publication of the American Society for Microbiology (ASM), challenge earlier studies suggesting as high as 40% of tumors are caused by viruses.[1]

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An increased potential
For years scientists believed viruses played a role in the development of maybe 10 to 20% of all human cancers. But in 2011, scientists at the Karolinska Institute in Sweden identified potential viral links to several cancers not previously associated with viruses. These cancers included brain tumors and prostate cancer, suggesting the real number of cancers associated with a specific virus could, potentially, be as high as 40%.

To better understand the role of DNA viruses in human cancers, researchers from the MD Anderson Cancer Centerin Houston, Texas, sequenced RNA from 3,775 malignant tumor samples from The Cancer Genome Atlasand then applied a robust bioinformatics algorithm to survey them for the presence of viral transcripts.

Those cancers not associated with DNA viruses included acute myeloid leukemia, cutaneous melanoma, low and high-grade gliomas of the brain (the latter killed Senator Edward Kennedy), and adenocarcinomas of the breast, colon and rectum, lung, prostate, ovaries, kidneys, and thyroid.

“These findings”, explains Xiaoping Su, Ph.D, Associate Professor, Bioinformatics & Comp Biology at The University of TexasMD Anderson Cancer Center and an author on the study, “Suggest that the earlier estimate that 40% of tumors are associated with or are virus-related should [actually] be much lower.The search for virus associations in these malignancies has consumed the efforts of many investigators,” she explains, implying that his large-scale effort will spare researchers fruitless investigations.

A framework for understanding
The study also provides the framework for understanding how viruses integrate into cancer subtypes such as hepatocellular cancer (HCC, also known as malignant hepatoma), the most common type of liver cancer. That might make it possible to personalize treatments by targeting genes that are located within known integration sites and that might be drivers of cancer initiation and progression. A key finding was that there are specific sites where viruses integrate into the host genome prior to initiating cancer, and that these sites are frequently located within particular host genes.

“This study highlights the importance of bioinformatics in defining the landscape of virus integration across cancer subtypes,” Su concludes.

For more information:
Khoury JD, Tannir NM, Williams MD, Chen Y, Yao H, Zhang J, et al. Landscape of DNA Virus Associations across Human Malignant Cancers: Analysis of 3,775 Cases Using RNA-Seq. J Virol. 2013 Aug;87(16):8916-26. doi: 10.1128/JVI.00340-13. Epub 2013 Jun 5. [Article][PubMed]

Photo:Xiaoping Su, Ph.D, Associate Professor, Bioinformatics & Comp Biology atThe University of TexasMD Anderson Cancer Centerand an author on the study. Photo/Image: Property of MD Anderson Cancer Center and protected by copyright laws.

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