Genomic analysis of metastatic XXXX .

@entity1 @entity986 @entity5 @entity2557 @entity957 @entity470 @entity876 @entity1082 @entity3 @entity68343 @entity817 @entity10160
PURPOSE: A rare 5% of cutaneous @entity957 (cSCC) metastasize, lack FDA-approved therapies, and carry a poor prognosis. Our aim was to identify recurrent genomic alterations in this little-studied population of metastatic cSCCs. EXPERIMENTAL DESIGN: We performed targeted sequencing of 504 @entity5 -associated genes on lymph node @entity3 in 29 @entity1 with cSCC and identified mutations and somatic copy-number alterations associated with metastatic cSCC. We determined significantly mutated, deleted, and amplified genes and associated genomic alterations with clinical variables. RESULTS: The cSCC genome is heterogeneous with widely varying numbers of genomic alterations and does not appear to be associated with @entity1082 . We found previously identified recurrently altered genes ( @entity876 , @entity986 , @entity68343 ) but also a wide spectrum of oncogenic mutations affecting RAS/RTK/ @entity10160 , squamous differentiation, cell cycle, and chromatin remodeling pathway genes. Specific mutations in known oncogenic drivers and pathways were correlated with inferior @entity1 outcomes. Our results suggest potential therapeutic targets in metastatic cSCC, including @entity10160 , @entity2557 , @entity817 , and @entity470 , similar to those reported in SCCs of the lung and head and neck, suggesting that clinical trials could be developed to accrue @entity1 with SCCs from multiple sites of origin. CONCLUSIONS: We have genomically characterized a rare cohort of 29 metastatic cSCCs and identified a diverse array of oncogenic alterations that can guide future studies of this disease. Clin Cancer Res; 21(6); 1447-56.   2015 AACR.
