Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky

Appalachian Kentucky (AppKY) is home to the highest incidence rate of lung cancer in US. Therefore, we characterized genomic alterations in squamous cell carcinoma (SQCC) from AppKY using whole exome sequencing of 51 subjects. In this preliminary analysis, we identified an average of 237 non-silent mutations per patient, and in contrast to The Cancer Genome Atlas (TCGA), we found that PCMTD1 (18%) and IDH1 (12%) were more commonly altered in our AppKY population. Using IDH1 and PCMTD1 as starting points, we identified functionally related genes and their protein-protein interaction partners, which provide new insights into cancer-specific pathways and helping to identify causes of AppKY lung cancer. These findings also suggest population differences in the genetics of lung SQCC between AppKY and US populations that have implications for personalized treatment. So in collaboration with the DT program, a clinical trial targeting the IDH1 R132H mutation is in development. Specifically, this KLCR proposal aims to investigate epigenetic and gene expression consequences of these genomic mutations unique to the AppKY population and identify new oncogenic mutations. The overarching hypothesis is that in-depth investigation of AppKY-specific mutations and related molecular phenotypes will identify novel signaling mechanisms of SQCC.