BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) Mutations in Distinct Subsets of Pancreatic Cancer: Potential Therapeutic Targets
作者： Eric S. Calhoun , Jessa B. Jones , Raheela Ashfaq , Volkan Adsay , Suzanne J. Baker
DOI: 10.1016/S0002-9440(10)63485-2
关键词:
摘要: The recognition of biologically distinct tumor subsets is fundamental to understanding tumorigenesis. This study investigated the mutational status serine/threonine kinase BRAF and cyclin E regulator FBXW7 (CDC4, FBW7, AGO, SEL10) related two pancreatic carcinoma subsets: medullary KRAS2-wild-type overexpressing tumors, respectively. Among carcinomas, 33% (3 9) contained V599E mutations; one which was identified in cancer cell line COLO357. 74 KRAS2-mutant no mutations were identified. KRAS2/BRAF wild-type within pathway members MEK1, MEK2, ERK1, ERK2, RAP1B, or BAD found. Using microarrays immunohistochemistry, we determined that 6% (4 46 5 100 independent panels) adenocarcinomas overexpress E. We potential mechanisms for this overexpression including amplification/gain CCNE1 gene copies Panc-1 Su86.86 lines a novel somatic homozygous mutation (H460R, 11 xenografts having allelic loss) FBXW7, accompanied by immunohistochemistry. Both functionally activate effectors important extend options therapeutic targeting kinases treatment phenotypically adenocarcinoma subsets.
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