Lung adenocarcinoma, the most common form of lung cancer, has been associated with characteristic genetic mutations as a result of work from The Cancer Genome Atlas (TCGA), run by the National Institutes of Health (NIH). Three-quarters of the samples analyzed by researchers, who published their findings in Nature, entitled, “Comprehensive molecular profiling of lung adenocarcinoma,” had mutations that increased activity in the RTK/RAS/RAF signaling pathway. As a result, drugs that already target these mutations may be introduced as new treatments for lung cancer patients.
“The integrated nature of TCGA analysis made these findings and their potential therapeutic implications possible,” said NIH Director Francis S. Collins, MD, PhD, in a news release from NIH. “We hope this lays the groundwork for future work in precision medicine.”
Mutations were examined using the genome, RNA, and proteins of 230 lung adenocarcinoma samples. An initial scan identified mutations in the RTK/RAS/RAF pathway in 62% of samples. These samples were classified as oncogene-positive, as the mutations were all found in oncogenes.
Additional alterations were found by analyzing DNA copy number changes due to deletion or amplification of DNA sections in the genome. Two amplifications were of oncogenes ERBB2 and MET, both part of the RTK/RAS/RAF pathway, which promotes cancer cell proliferation and survival when it is continuously activated. Further analysis showed the NF1 and RIT1 genes, both associated with RTK/RAS/RAF, were also mutated in some samples. Overall, eighteen genes were found to be mutated.
“This most recent TCGA study again demonstrates the power, depth and breadth of TCGA data,” said National Human Genome Research Institute Director Eric Green, MD, PhD. “These results give us important new genomic insights into the development and behavior of an important form of cancer.”
“It is quite striking that we have now identified an actionable mutation in over 75% of patients with lung adenocarcinoma, a significant improvement from a decade ago,” added Matthew Meyerson, MD, PhD, a lead investigators on the project from Harvard Medical School, Dana-Farber Cancer Institute, and The Broad Institute.
A similar study was published in 2012 that used TCGA analysis for the less common squamous cell carcinoma form of lung cancer. “Combined with the earlier TCGA analysis of squamous lung cancers, we now have a comprehensive understanding of many of the genetic pathways that lead to cancers of the lung,” said National Cancer Institute Director Harold Varmus, MD. “Based on this knowledge, we can now seek better pathway inhibitors to improve patient outcomes. However, for the time being, stopping smoking or never starting remain the most reliable ways to reduce the number of deaths due to lung cancer.”