The frequencies and clinical implications of mutations in 33 kinase-related genes in locally advanced rectal cancer.

3549 Background: Locally advanced rectal cancer, LARC (T3/4 and/or N+) is currently treated with pre-operative chemoradiotherapy (pCRT), but responses are not uniform. The phosphatidylinositol 3-kinase (PI3K), MAP-kinase (MAPK) and related pathways have been implicated in rectal cancer tumorigenesis. Here, we investigated the association between genetic variations in these pathways and clinical outcomes in LARC. Methods: We genotyped a total of 234 Single Nucleotide Polymorphisms (SNPs) including potentially clinically relevant mutations in 33 cancer related genes including PIK3CA, PIK3R1, AKT, STK11, KRAS, BRAF, MEK, CTNNB1, EGFR, MET and NRAS using the Sequenom platform. DNA samples utilized herein were extracted from pre-treatment rectal cancer biopsies of 201 patients who were then treated with long-course pCRT followed by surgical resection. Results: 62 different mutations were detected in 15 genes, with the highest frequencies occurring in KRAS (n=93, 47%), PIK3CA (n=29, 14%), MET (n=27, 13%), STK11...