Most Common Tumors Are Driven by Two to Six DNA Mutations
A genetic analysis of 3,281 tumors from 12 cancer types, including breast, lung, endometrial, glioblastoma multiforme, ovarian, colon, and acute myeloid leukemia, has found 127 significantly mutated genes that appear to be involved in either cancer initiation or progression. Although the average number of mutations in these significantly mutated genes varied across tumor types, most tumors had between two and six mutations, indicating that the number of driver mutations required during oncogenesis is relatively small. The study appears in Nature.
The study was conducted by Li Ding, PhD, and colleagues from The Genome Institute at Washington University in St. Louis, and is part of The Cancer Genome Atlas (TCGA) Pan-Cancer project. The researchers found that the most frequently mutated gene in the Pan-Cancer cohort was TP53 (42% of samples), predominantly in serous ovarian (95%) and serous endometrial carcinomas (89%). TP53 mutations were also associated with basal subtype breast tumors. The second most commonly found mutated gene was PIK3CA, occurring frequently (> 10%) in most cancer types, with the exception of ovarian, kidney, lung adenocarcinoma, and acute myeloid leukemia. The finding, wrote the researchers, “suggests common therapeutic strategies might be applied for these tumors.”
Genes Associated With Poorer Survival
After taking cancer type, patient age, and gender as covariates, the researchers identified seven significant genes with mutations associated with detrimental outcome, including BAP1, DNMT3A, HGF, KDM5C, FBXW7, BRCA2, and TP53.
“Although a common set of driver mutations exists in each cancer type, the combination of drivers within a cancer type and their distribution within the founding clone and subclones varies for individual patients. This suggests that knowing the clonal architecture of each patient’s tumor will be crucial for optimizing their treatment,” wrote the researchers.
According to the study, given the rapid rate at which TCGA and the International Cancer Genome Consortium projects are generating genomic data, there is a “reasonable chance” of identifying most core cancer genes and pathways and tumor type–specific genes and pathways in the “near term.”
Having a catalog of cancer’s genetic mutations could be helpful for prognosis at various clinical time points and in the development of personalized treatment for patients, according to the study.
The study authors reported no competing financial interests.
Funding was provided by the National Cancer Institute, the National Human Genome Research Institute, and the National Science Foundation.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
