Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis
Journal article, 2006
BACKGROUND & AIMS: Gain-of-function mutations in the KIT receptor tyrosine kinase gene and rare mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene are important events in gastrointestinal stromal tumor (GIST) development. Different mutations are reportedly associated with distinctive phenotypes and possibly clinical behavior. We investigated the correlation among mutation type, phenotype, and clinical course in a preimatinib, population-based series of GIST with long-term follow-up. METHODS: Genomic DNA from 177 GIST patients was analyzed for KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 mutations using denaturating high-performance liquid chromatography and bidirectional sequencing. RESULTS: KIT exon 11 mutations were detected in 101 of 177 GIST (61 deletions, 23 missense mutations, and 17 duplications); wild-type (WT) KIT and PDGFRA were detected in 63; KIT exon 9 and exon 17 mutations in 6 and 1, respectively; and PDGFRA exons 12 and 18 mutations in 3 each. GIST >5 cm vs GIST
Proto-Oncogene Proteins c-kit/*genetics
Sensitivity and Specificity
Retrospective Studies
Middle Aged
Humans
Neoplastic
*Mutation
Cohort Studies
Platelet-Derived Growth Factor alpha/*genetics
Tumor Markers
Gene Expression Regulation
Male
Biological
Aged
Missense
Receptor
Exons/genetics
Gastrointestinal Stromal Tumors/*genetics/*mortality/therapy
DNA Mutational Analysis
Survival Rate
Prognosis
Probability
Adult
Risk Assessment
Female
Gene Deletion
Author
Johanna Andersson
University of Gothenburg
Per Bümming
University of Gothenburg
Jeanne Meis-Kindblom
University of Gothenburg
H. Sihto
Helsinki University Central Hospital
N. Nupponen
Helsinki University Central Hospital
H. Joensuu
Helsinki University Central Hospital
Anders Odén
University of Gothenburg
Chalmers, Mathematical Sciences
B. Gustavsson
Novartis International AG
Lars-Gunnar Kindblom
University of Gothenburg
Bengt E Nilsson
University of Gothenburg
Gastroenterology
0016-5085 (ISSN) 1528-0012 (eISSN)
Vol. 130 6 1573-81Subject Categories (SSIF 2011)
MEDICAL AND HEALTH SCIENCES
DOI
10.1053/j.gastro.2006.01.043
PubMed
16697720