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New gene mutations in lung adenocarcinoma identified
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In a recent study, researchers identified 26 genes with high frequency mutations in human lung adenocarcinomas. The results may broaden the range of potential therapeutic options for treating the disease, according to the researchers from Dana-Farber Cancer Institute, Broad Institute of Harvard, MIT and other sites nationwide.
They conducted a collaborative study to detect somatic mutations in 188 human lung adenocarcinomas. More than 1,000 somatic mutations were revealed using DNA sequencing of 623 genes with known or potential relationships to cancer. The researchers identified 26 genes mutated at high frequencies. Among them, NF1 was the most prominently mutated tumor suppressor gene; 16 mutations were found in 13 patients.
Additional tumor suppressor genes were found to have mutations, including RB1, ATM and APC. These four genes have not before been associated with lung cancer, according to a press release.
The researchers identified nine mutations in ERBB4 — two putatively deleterious relating to the protein tyrosine kinase domain and five clustered in the receptor ligand binding domain, indicating the gene’s involvement in lung cancer. Other discovered mutations clustered in several groups of tyrosine kinase genes, including the EGF, EPH, FGF, NTRK and VEGF receptor gene families.
Many of the newly identified mutated genes are targeted by copy number alterations and/or gene expression changes, according to the study. Additionally, genes from the MAPK, p53, Wnt, cell cycle and mTOR signaling pathways may be linked to the disease due to an excess of mutations and copy number alterations.
According to the researchers, the results also demonstrated that lung adenocarcinomas are heterogeneous and have diverse combinations of mutations, but with commonalities in the main pathways affected by the mutations. The researchers wrote that varied mutation rates across tumor samples may be influenced by DNA mismatch repair defects and other clinical features.
Nature. 2008; 455:1069-1075.