Somatic Genome Changes in Human Non–Small Cell Lung Cancers

Abstract

Human lung cancers are characterized by a high degree of somatic genome alterations, including mutations, copy number changes, and translocations. These alterations have significant implications for the current scope of targeted therapy, especially with regards to activation of the receptor tyrosine kinase/Ras/Raf pathway in lung adenocarcinoma. Mutation burden is associated. Analysis of whole exome sequences of non–small cell lung cancers has revealed somatic mutations with a potential relation to immunotherapy response, including loss-of-function mutations in the HLA-A, JAK2, and B2M genes. Analysis of whole genome sequences of non–small cell lung carcinomas has revealed somatic duplication of super-enhancer elements near the MYC and KLF5 genes. Recurrent somatic indels are found in and near all of the surfactant protein genes. Multiple novel mechanisms of genome alteration continue to be discovered in non–small cell lung carcinoma, with potential therapeutic and diagnostic implications.