Abstract LB-151: Targeted gene resequencing in a K-ras-dependent mouse model of metastatic lung adenocarcinoma

Abstract

Abstract Progression of lung adenocarcinoma to invasive, metastatic disease is responsible for the majority of deaths from lung cancer and remains incompletely understood. We have developed a genetically-engineered mouse model of lung adenocarcinoma initiated by mutant K-ras and loss of p53 that develops invasive, metastatic disease. In order to identify the genes and pathways that cooperate with oncogenic K-ras and loss of p53 to contribute to tumor development, progression, and metastasis, we have utilized in situ exon capture and massively parallel DNA sequencing to identify somatically-acquired point mutations in advanced stage murine lung adenocarcinoma cell lines. We have initially chosen a target set of 1283 cancer-relevant genes to develop our capture, sequencing, and bioinformatics platforms. Using tumor cell lines derived from K-ras-dependent tumors, we have successfully developed and refined these methods and have identified somatic mutations in our test samples. These mutations have been validated by conventional methods in the tumor cell line and founder tumor DNA. We have developed a production phase target gene set consisting of 1909 cancer-relevant genes and have initiated capture and sequencing of additional murine lung adenocarcinoma cell lines and tumors. We believe these datasets will expand the understanding of the biology of tumor progression and serve as an important biological filter for human cancer gene re-sequencing efforts. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-151.