Gastrointestinal stromal tumors with exon 8 c-kit gene mutation might occur at extragastric sites and have metastasis-prone nature.
Gastrointestinal stromal tumors with exon 8 c-kit gene mutation might occur at extragastric sites and have metastasis-prone nature.
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具有外显子8 c-kit基因突变的胃肠道间质瘤可能发生在胃外部位，并且具有转移倾向。
DOI：
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发表时间：
2014
影响因子：
1.4
通讯作者：
S. Hirota
中科院分区：
文献类型：
--
作者：
Takashi Ito;M. Yamamura;T. Hirai;T. Ishikawa;T. Kanda;T. Nakai;Mizuka Ohkouchi;Y. Hashikura;K. Isozaki;S. Hirota
胃肠道间质瘤（gist）是人类肠道最常见的间质肿瘤。大多数散发性gist具有c-kit基因的体细胞功能获得性突变。突变常在外显子11，有时在外显子9，很少在外显子13或17。最近，外显子8 c-kit基因突变在散发的gist中报道的比例很小。我们还在大约1000例散发性gist中发现了3例外显子8 c-kit基因突变的gist。在本报告中，我们展示了这些gist的临床病理资料。1例缺失天冬氨酸密码子419,2例417密码子3个氨基酸被替换为酪氨酸。前者是最近在2例GIST病例中报道的相同突变，而后者尚未在任何GIST中报道。3例均发生胃外部位，其中2例有远处转移。由于剩余的病例被认为是复发的高风险，伊马替尼辅助治疗没有转移的证据。我们的研究结果证实了散发性gist的外显子8突变是微小的，但实际上存在异常，并表明此类gist具有胃外发展和易转移的特征。由于外显子8突变似乎对伊马替尼非常敏感，因此在gist中，包括c-kit基因外显子8的准确基因分型对于预测在不可切除/转移和辅助情况下对伊马替尼的反应是必要的。
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the human gut. Most sporadic GISTs have somatic gain-of-function mutations of the c-kit gene. The mutations are frequently found at exon 11, sometimes at exon 9 and rarely at exon 13 or 17. Recently, exon 8 c-kit gene mutations were reported in very minor proportion of sporadic GISTs. We also found 3 GISTs with exon 8 c-kit gene mutations in approximately 1,000 sporadic GISTs examined. In the present report, we showed the clinicopathological data of those GISTs. One case had a deletion of codon 419 of aspartate, and 2 cases had a substitution of 3 amino acids of codon 417 to codon 419 to tyrosine. The former was the same mutation recently reported in 2 GIST cases, but the latter has not been reported in any GISTs. All three cases occurred at extragastric sites and two of three showed distant metastasis. Since the remaining case was regarded as high risk for recurrence, imatinib adjuvant treatment has been done without evidence of metastasis. Our results confirmed the idea that exon 8 mutations are minor but actually existing abnormalities in sporadic GISTs, and suggested that such GISTs have a feature of extragastric development and a metastasis-prone nature. Since the exon 8 mutations appeared to be really sensitive to imatinib as shown in the present case study, accurate genotyping including exon 8 of the c-kit gene is necessary in GISTs to predict response to imatinib in both the unresectable/metastatic and adjuvant settings.
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DOI：
--
发表时间：
2000-10
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
E. Buchdunger;C. Cioffi;N. M. Law;D. Stover;Sayuri Ohno-Jones;B. Druker;N. Lydon
通讯作者：
E. Buchdunger;C. Cioffi;N. M. Law;D. Stover;Sayuri Ohno-Jones;B. Druker;N. Lydon
影响因子：
6
作者：
Tian, QS;Frierson, HF;Moskaluk, CA
通讯作者：
Moskaluk, CA
影响因子：
29.4
作者：
Hartmann, K;Wardelmann, E;Longley, BJ
通讯作者：
Longley, BJ
影响因子：
45.3
作者：
Curtin, John A.;Busam, Klaus;Bastian, Boris C.
通讯作者：
Bastian, Boris C.