Association of platelet-derived growth factor receptor α mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors
Association of platelet-derived growth factor receptor α mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors
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DOI：
10.1016/s1525-1578(10)60510-7
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发表时间：
2004-08-01
影响因子：
4.1
通讯作者：
Pietsch, T
中科院分区：
文献类型：
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作者：
Wardelmann, E;Hrychyk, A;Pietsch, T
大多数胃肠道间质瘤(GIST)携带编码受体酪氨酸激酶KIT的KIT基因的激活突变。在之前的一项研究中，我们能够证明KIT突变(野生型GIST)的缺乏与重要上皮样肿瘤成分的存在之间存在关联。最近的一项研究描述了PDGFRpha突变在试剂盒中的发生。因此，我们用单链构象多态分析和测序的方法对87个GIST进行了PDGFRpha基因热点区域的突变研究，并将PDGFRA的状态与病理形态数据相关联。我们检测到20例外显子18突变，但没有外显子12突变。突变位于PDGFRA的第二个蛋白激酶结构域，有16个点突变，4个较大的9~12个碱基缺失。所有有PDGFRA基因突变的病例均发现野生型Kit位于共同的突变区域，即外显子9和11。最有趣的是，PDGFRA突变的发生与上皮样或混合形态(18/20，P=0.0001)和胃的位置(ALL，P=0.0008)显著相关。我们的数据表明，GIST代表不同的实体，在遗传、生物学和形态特征上不同。
Most gastrointestinal stromal tumors (GISTs) carry activating mutations of the KIT gene encoding the receptor tyrosine kinase KIT. In a previous study we were able to show an association between the lack of KIT mutations (wild-type GISTs) and the presence of a significant epithelioid tumor component. A very recent study described the occurrence of PDGFRalpha mutations in KIT wt GISTS. Therefore, we studied a panel of 87 GISTs for mutations in the hot spot regions of the PDGFRalpha gene with single strand conformation polymorphisin analysis and sequencing and correlated the PDGFRa status with pathomorphological data. We detected 20 cases with exon 18 mutations but none with exon 12 mutations. The mutations were located in the second kinase domain of PDGFRa with 16 point mutations, and four larger deletions of 9 to 12 bp. All cases with mutations in the PDGFRa gene revealed wild-type KIT in common regions of mutation, ie, exons 9 and 11. Most interestingly, the occurrence of PDGFRa mutations was significantly associated with a higher frequency of epithelioid or mixed morphology (18 of 20 cases, P < 0.0001) and gastric location (all cases, P = 0.0008). our data indicate that GISTs represent distinctive entities, differing in genetic, biological, and morphological features.