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Delving Into the Cervical Cancer Genome


By Aaron Krol

December 27, 2013 | The first genome-wide study of cervical cancer mutations in a large cohort of patients was published this week in Nature. The program, undertaken through the Slim Initiative for Genomic Medicine in the Americas (SIGMA) and featuring an international team of researchers from Mexico, the U.S. and Norway, sequenced the whole exomes of over a hundred patients and their cervical tumors in order to identify key mutations involved in this cancer type. “Cervical cancer remains one of the most common deadly cancers around the world, although today vaccination offers the promise of vastly decreasing the number of cervical cancer cases,” said Dr. Matthew Meyerson, a senior co-author of the paper and member of both the Broad Institute and the Dana Farber Cancer Institute, in an email to Bio-IT World. “Finding new genomic alterations in cervical cancer, as we have just reported, offers the promise that new treatments can be tested for patients with life-threatening cervical cancers.”

The researchers found over a dozen mutations that regularly occur in cervical cancer, including some that have shown promise as drug targets in other cancer types. However, Dr. Meyerson points out that cervical cancer appears to be highly heterogeneous, with numerous different driver mutations implicated in the disease, meaning that a single therapy is unlikely to emerge from genetic studies. Instead, individual variants will have to be matched to treatments as new drugs are developed and tested.

The common denominator in cervical cancer is the human papillomavirus (HPV), which is the root cause of virtually all cases of the disease. For this reason, the researchers also sequenced whole transcriptomes of many subjects’ tumors. These measurements of gene expression can help to pinpoint where the virus has copied its genome into the cellular DNA, and how this affects the cellular machinery. “It turns out that HPV not only promotes cancer directly with the activity of its own genes,” said Dr. Meyerson, “but could also promote cancer by affecting the expression of cellular genes. This could help to explain in part why some pre-cancers of the cervix develop into cervical cancer while others do not.” The team discovered that HPV insertion was commonly associated with higher levels of gene expression, illuminating the process by which certain HPV infections gradually lead to cancer, while the majority are harmless.

Conducted under the SIGMA umbrella, this study is part of an initiative to include lower-resource countries in the Americas in cutting-edge genetic research, ensuring that the genetic diversity of these countries is not neglected when searching for the genes involved in disease. The National Institute of Genomic Medicine in Mexico City, and the University of Nuevo León in Monterrey, were major partners in the study, and contributed one of the two patient cohorts to be sequenced. Globally, cervical cancer accounts for one in ten cancer deaths in women, a number that public health authorities hope will decrease as vaccination campaigns pick up steam.

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