Novel V600E BRAF mutations in imatinib‐naive and imatinib‐resistant gastrointestinal stromal tumors

• DOI: 10.1002/gcc.20589
• Publication Date: 2008-07-09T18:06:58Z
• Authors: Narasimhan P. Agaram; Grace C. Wong; Tianhua Guo; Robert G. Maki; Samuel Singer; Ronald P. DeMatteo; Peter Besmer; Cristina R. Anton...
• Keywords: PDGFRA; Proto-Oncogene Proteins c-kit; V600E; Stromal tumor

Abstract BRAF and NRAS are commonly mutated in cancer represent the most frequent genetic events malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT harbor mutations. Although gastrointestinal stromal tumors (GISTs) exhibit activating mutations either or PDGFRA , about 10% cases lack these genes. It is our hypothesis following melanoma model that may play role wild‐type GIST pathogenesis. Alterations RAS/MEK/ERK pathway also be involved development imatinib resistance GIST, particularly lacking secondary Imatinib‐naive GISTs from 61 patients, including 15 children 28 imatinib‐resistant without were analyzed. Screening for hot spots (exons 11 15) 2 3) performed. A exon V600E identified 3 who shared similar clinical features, being 49‐ 55‐years‐old females having their located small bowel. The strongly immunoreactive had high risk malignancy. An identical mutation one resistant defined mechanism drug resistance. In conclusion, we primary 7% adult KIT/PDGFRA ‐mutated show predilection bowel location could an alternative Kinase inhibitors targeting effective therapeutic options this molecular subset. © 2008 Wiley‐Liss, Inc.