C-KIT mutations were closely associated with the response to Imatinib in Chinese advanced gastrointestinal stromal tumor patients
C-KIT mutations were closely associated with the response to Imatinib in Chinese advanced gastrointestinal stromal tumor patients
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DOI：
10.1007/s12032-012-0308-7
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发表时间：
2012-12-01
期刊：
影响因子：
3.4
通讯作者：
Shen, Lin
中科院分区：
文献类型：
--
作者：
Gao, Jing;Dang, Yunzhi;Shen, Lin
探讨中国晚期胃肠道间质瘤（GIST）患者C-KIT/PDGFR α突变与伊马替尼疗效或生存期的相关性。临床数据和石蜡包埋的肿瘤标本收集自158例接受伊马替尼一线治疗的晚期GIST患者。通过PCR扩增和桑格测序对C-KIT基因（外显子9、11、13和17）和PDGFR α基因（外显子12和18）进行突变分析。本研究共发现135例携带C-KIT突变的患者（11号外显子突变：108例; 9号外显子突变：23例; 13号外显子突变：2例; 17号外显子突变：2例）和1例携带PDGFR α突变（18号外显子）的患者。22例既无C-KIT突变也无PDGFR α突变的患者（13.9%）被命名为野生型。突变型患者（n = 136）的缓解率（64.7 vs. 36.4%，P = 0.000）和中位无进展生存期（28 vs. 8个月，P = 0.000）显著高于野生型患者（n = 22）。此外，11号外显子突变患者（n = 108）、9号外显子突变患者（n = 23）和野生型患者（n = 22）的缓解率和中位无进展生存期分别为68.5%、47.8%和36.4%（P = 0.001）以及31个月、13个月和8个月（P = 0.000）。11号外显子缺失突变、点突变和混合型突变患者的缓解率或中位无进展生存期无显著差异。C-KIT突变与中国晚期GIST患者伊马替尼疗效和无进展生存期密切相关。伊马替尼的其他预测标志物将进一步研究。
To investigate the correlation between C-KIT/PDGFR alpha 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 PDGFR alpha 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 PDGFR alpha mutation (exon 18) were found in this study. Twenty-two patients (13.9 %) with neither C-KIT nor PDGFR alpha 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.