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Cutaneous Squamous Cell Carcinoma: Integrating Germline and Somatic Alterations that Underlie Tumor Progression

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States, affecting over a million people annually, and with significant mortality due to metastasis. The overall scientific objective of this study is to identify and integrate novel tumor mutational data with previously characterized information on host genetic risk factors and clinical risk factors to better understand how cancer risk alleles contribute to the development of cSCCs capable of metastasis. We analyze 290 cSCCs (145 primary cSCCs) that progressed to metastasis and 145 non-metastatic primary cSCCs arising in the well characterized GERA cohort to provide a comprehensive landscape of genomic alterations in cSCCs. The aims of the study are: a) characterize the somatic genome and transcriptome of metastatic and non-metastatic cSCCs, b) integrate somatic mutational analysis with environmental exposure data, and c) develop a risk prediction tool for metastatic-cSCC that integrate genomic and clinical data.