Researchers from The Cancer Genome Atlas (TCGA) Research Network have identified novel mutations in a well-known cancer-causing pathway in lung adenocarcinoma, the most common subtype of lung cancer. Knowledge of these genomic changes may expand the number of possible therapeutic targets for this disease and potentially identify a greater number of patients with treatable mutations, because many potent cancer drugs that target these mutations already exist.
In a study published online in Nature, researchers examined the genomes, RNA, and some protein from 230 lung adenocarcinoma samples. In three-quarters of the samples, they ultimately identified mutations that put a cell signaling pathway known as the RTK/RAS/RAF pathway into overdrive. Mutations affecting the RTK/RAS/RAF pathway can cause it to become stuck in the “on” state. As a result, signals that promote cancer cell proliferation and survival are produced continuously. However, some currently available drugs curb aberrant activity of this pathway and prompt therapeutic responses in patients.
In the group’s initial scan of tumor samples, researchers identified gene mutations that would increase RTK/RAS/RAF pathway activity in 62% of the samples. The affected genes are oncogenes, genes that have the potential to cause cancer when mutated or expressed at high levels. Consequently, these tumor samples were classified as oncogene-positive.
To identify additional alterations, the investigators looked at DNA copy number changes, or changes in gene number resulting from the deletion or amplification (multiplication) of sections of DNA in the genome. In doing so, they detected amplification of two oncogenes, ERBB2 and MET, which are part of the RTK/RAS/RAF pathway. Gene amplification usually leads to increased expression of the encoded protein in cells. Now that these amplifications have been identified, clinicians may be able to treat patients whose tumors have specific gene changes with drugs currently available or under development. Read the study.
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