TCGA researchers uncover differences between tumors with and without HPV infection

The study by The Cancer Genome Atlas (TCGA) researchers analyzed the genomes of 279 head and neck cancer tumors. They identified subtypes of head and neck cancer based on their genomic characteristics, changes in smoking-related tumors, as well as genomic differences in head and neck cancer tumors linked to HPV, the most commonly sexually transmitted disease in the United States.

The findings were published online Wednesday in the journal Nature. Researchers hope the findings will help lead to potential new therapies and the identification of markers that can help identify patients likely to respond to a particular therapy, as well as help direct the best course of treatment for patients.

"The rapid increase in HPV-related head and neck cancers, noticeably in oropharyngeal tumors, has created an even greater sense of urgency in the field," said D. Neil Hayes, MD, MPH, senior author of the study report, an associate professor of medicine at the University of North Carolina School of Medicine and a member of UNC Lineberger. Oropharyngeal cancer starts in the oropharynx, which is the part of the throat behind the mouth. "We're uncovering differences between tumors with and without HPV infection, and these new data are allowing us to rethink how we approach head and neck cancers."

Smoking and alcohol use are main risk factors for head and neck cancer, according to the National Cancer Institute (NCI). But studies have shown that HPV-linked oropharyngeal cancer cases are on the rise. About 9,000 new oropharyngeal cancer cases are estimated to have been caused by HPV in the United States each year, according to the Centers for Disease Control and Prevention.

Comparatively, there were an estimated 55,000 new cases last year of all types of head and neck cancer, which include tumors of the mouth, throat, voice box, nasal cavity and salivary gland.1 In North Carolina, there were 1,850 new cases of head and neck cancer in 2012, which was up about 3 percent from 2011.2

In the HPV positive tumors in their sample, they found tumors with deletions and mutations of a gene called TRAF3, which is involved in anti-viral response. The researchers also found alterations of the FGFR3 gene and mutations in the PIK3CA gene in HPV positive tumors, which are also found in a much broader set of mutations in smoking-related tumors. PIK3CA has already been shown to be associated with HPV, Hayes said, but he said they showed the link clearly in their study.

And the study found that while the EGFR (epidermal growth factor receptor) gene is frequently altered in HPV-negative tumors in smokers, it is rarely abnormal in HPV-positive tumors.

They found that many of the head and neck cancer tumors in the study had alterations in a group of genes for certain growth factor receptors such as EGFR and FGFR, signaling molecules, and cell division regulation.

"So this is a set of alterations that, at some level, many people think are drug-able," Hayes said. He called attention to the study's findings for one gene in particular, CCND1, that's involved in cell division regulation. Hayes said the gene is involved in a drug-able pathway, and a potential drug is in development for it.

In addition to helping understand genomic changes in head and neck cancer, Hayes also said the study's findings may also help further the understanding of other cancer types.

And while Hayes said TCGA efforts have helped create a "parts list" of genomic alternations in a range of cancers, he said there are cancer types for which more genomic mapping is needed.

"Just like in a car manual, you need to know what kind of car you have and what the parts are to know how to put it back together," Hayes said. "We really have built a parts manual for what's broken in cancer so that we can start addressing it in a logical and a real way."

The Cancer Genome Atlas is supported and managed by the NCI and the National Human Genome Research Institute. The TCGA network includes researchers at institutions around the country and globe.

As national leaders in TCGA, UNC Lineberger scientists have been involved in multiple, individual tissue type studies as well as the largest, most diverse tumor genetic analysis ever conducted to date. UNC has done RNA sequencing work for those projects, among other contributions.

Source:

University of North Carolina Health Care

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