title: C-KIT mutations were closely associated with the response to Imatinib in Chinese advanced gastrointestinal stromal tumor patients.
abstract: To investigate the correlation between C-KIT/PDGFRα mutations and Imatinib response or survival in Chinese advanced gastrointestinal stromal tumor (GIST) patients. Clinical data and paraffin-embedded tumor specimens were collected from 158 advanced GIST patients receiving first-line Imatinib. Mutation analyses of C-KIT gene (Exons 9, 11, 13, and 17) and PDGFRα gene (exons 12 and 18) were performed by PCR amplification and Sanger sequencing. A total of 135 patients harboring C-KIT mutations (exon 11 mutation: 108; exon 9 mutation: 23; exon 13 mutation: 2; exon 17 mutation: 2) and one patients carrying PDGFRα mutation (exon 18) were found in this study. Twenty-two patients (13.9 %) with neither C-KIT nor PDGFRα mutations were named as wild type. The response rate (64.7 vs. 36.4 %, P = 0.000) and median progression-free survival (28 vs. 8 months, P = 0.000) of mutant patients (n = 136) were significantly higher than those of wild-type patients (n = 22). Moreover, the response rate and median progression-free survival in patients with exon 11 mutations (n = 108), exon 9 mutations (n = 23), and wild-type patients (n = 22) were 68.5, 47.8, and 36.4 % (P = 0.001), and 31 months, 13 months, and 8 months (P = 0.000), respectively. No significant differences of response rate or median progression-free survival were seen in patients with exon 11 deletion mutations, point mutations, and mixed-type mutations. C-KIT mutations were closely associated with Imatinib response and progression-free survival of Chinese advanced GIST patients. Other predictive markers for Imatinib would be further investigated.
authors: Key Laboratory of Carcinogenesis and Translational Research, Department of GI Oncology, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China. gaojing_pumc@yahoo.com.cn
authors: Jing
authors: J
authors: Gao
authors: Yunzhi
authors: Y
authors: Dang
authors: Naiping
authors: N
authors: Sun
authors: Jian
authors: J
authors: Li
authors: Lin
authors: L
authors: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People; D001549:Benzamides / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit