Data uncover genomic signatures of most common lung cancer

Specific genetic mutations in an ear-marked pathway now have been implicated in the development of lung adenocarcinoma, the most prevalent subtype of lung cancer, according to a study published online July 9 in Nature. The discovery of these mutations could hone drug targets for new therapies down the road.

The study was a massive collaborative effort by The Cancer Genome Atlas (TCGA) Research Network and was funded by both the National Cancer Institute and the Human Genome Research Institute. The analysis includes an evaluation of 230 cases of lung adenocarcinoma. Researchers noted mutation profiles, mRNA, miRNA, protein expression, DNA methylation, copy number alterations and structural rearrangements and found key mutations within the RTK/RAS/RAF pathway to be worthy of dedicated research due to their influence on cellular proliferation and survival.

“In recent years, the treatment of lung adenocarcinoma has been advanced by the development of multiple therapies targeted against alterations in the RTK/RAS/RAF pathway,” wrote Matthew L. Meyerson, MD, PhD, director of the Center for Cancer Genome Discovery from the Dana-Farber Cancer Institute and a professor of pathology at Harvard Medical School in Boston, and colleagues. “We nominate amplifications in MET and ERBB2 as well as mutations of NF1 and RIT1 as driver events specifically in otherwise oncogene-negative lung adenocarcinomas.”

Said genetic factors were seen to increase the fraction of adenocarcinoma from 62 percent to 76 percent. This means 76 percent of adenocarcinomas of the lung could be characterized by alterations in MET, ERBB2, NF1 and/or RIT1.

The researchers noted that while most lung adenocarcinomas could be activating this pathway in one way or another, only the subset reveal tonic pathway activation down to the level of proteins. This could be an indication of heterogeneity between lung tumors. The results point to the potential benefits of drugs that inhibit ERBB2/HER2 and MET mechanisms within the pathway.

This research is a continuation of a study of genetic mutations in squamous cell carcinoma that was published in 2012. Collectively the analyses add to researchers' understanding of the underpinnings of lung cancer pathology.