Systematic and comprehensive genomic study of cervical cancer completed
Researchers from Boston, Massachusetts; Mexico; and Norway have completed a comprehensive genomic analysis of cervical cancer in two patient populations. The study identified recurrent genetic mutations not previously found in cervical cancer, including at least one for which targeted treatments have been approved for other forms of cancer. The findings also shed light on the role human papillomavirus (HPV) plays in the development of cervical cancer.
The study, which appeared in Nature (2014; doi:10.1038/nature12881), addresses a public health concern of global significance: cervical cancer is the second most common cancer in women and is responsible for approximately 10% of cancer deaths in women—particularly in developing countries where screening methods are not readily accessible. Almost all cases of the disease are caused by exposure to HPV and it is expected that vaccination efforts targeting HPV will decrease cervical cancer cases over time. In the meantime, however, the disease remains a significant threat to women's health.
"Cancer is a disease that affects the whole world, and one question that always arises is: is a given cancer type similar or different across populations?" explained Matthew Meyerson, MD, PhD, one of the paper's co-senior authors. Meyerson is a professor of pathology and medical oncology at Dana-Farber Cancer Institute and a senior associate member of the Broad Institute in Boston. "While we don't have the complete answer yet in this case, what we are seeing is that, in two different populations, the causes of cervical cancer are similar and, fundamentally in both cases, it comes down to HPV-genome interaction."
To investigate the genomic underpinnings of the disease, the team performed whole exome sequencing, which examines the genetic code in the protein-coding regions of the genome, on samples from 115 cervical cancer patients from Norway and Mexico. In some cases, the researchers also conducted whole genome sequencing (analyzing the genetic code across the entire genome) or transcriptome sequencing (focusing on gene expression). In each case, the researchers compared genomic data derived from cervical cancer tumors with genomic data from healthy tissue from the same individual to determine what may have gone wrong—or mutated—in the genome to allow the cancer to develop. The mutations identified in tumors but not in healthy tissues from the same persons are referred to as somatic mutations.
The study identified 13 mutations that occurred frequently enough across the samples to be considered significant in cervical cancer. Eight of these mutations had not been linked to the disease previously, and two had not previously been seen in any cancer type.
Notable findings included somatic point mutations in the gene ERBB2 (also known as human epidermal growth factor receptor 2 [HER2] and common in breast cancer), a novel mutation in the gene mitogen-activated protein kinase 1 (MAPK1), and mutations in genes affecting the immune system. The researchers were particularly enthused about potential therapeutic targets related to theERBB2 gene mutations.
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