Journal
ANNALS OF GASTROENTEROLOGICAL SURGERY
Volume 6, Issue 2, Pages 241-248Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ags3.12527
Keywords
gastrointestinal stromal tumor; genotype; imatinib-naive; KIT; PDGFRA
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Funding
- Kanagawa Prefectural Hospital Organization
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The study found that different types of KIT gene mutations are associated with the prognosis of GIST patients, with deletions and deletion-insertion mutations clearly linked to worse survival outcomes, while duplications and substitution mutations are associated with better survival.
Background Most gastrointestinal stromal tumors (GIST) harbor a mutation in KIT or platelet-derived growth factor receptor alfa (PDGFRA). Although genotyping is a useful predictive marker of tyrosine kinase inhibitors, whether it can predict prognosis remains controversial. Methods Data on 402 patients with GIST who underwent macroscopically complete surgery and received no neoadjuvant/adjuvant therapy were selected from a prospective GIST database at the three, participating hospitals. The types and locations of KIT and PDGFRA mutations were analyzed by direct sequencing of the amplified genes. The association between the genotypic characteristics and prognosis was then examined. Results Tumor genotypes were analyzed in 398 of 402 (99%) patients, and 120 mutation patterns were identified. KIT mutations had broad malignancy potential which differed according to the type of mutation. Deletion and deletion-insertion type mutations were associated with worse RFS while duplication and substitution type mutations were associated with favorable RFS KIT deletion/deletion-insertion, including codons 557 and 558, were especially associated with worse RFS on multivariate analysis both of all the patients and those with KIT mutations. Conclusions Specific GIST genotypes were significantly associated with a risk of recurrence. Genotype analysis may be useful for predicting the prognosis and determining the indications for adjuvant imatinib in patients with GIST.
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