Genetic evolution in metastatic lymph nodes of lung cancer

Tumor heterogeneity influences the clinical outcome of cancer patients, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six lung cancer patients using whole exome sequencing and RNA-seq. Although somatic single nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomical location of the tumors. Four out of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer.

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