GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology
GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology
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DOI：
10.1038/labinvest.3700360
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发表时间：
2006-01-01
影响因子：
5
通讯作者：
Miettinen, M
中科院分区：
文献类型：
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作者：
Lasota, J;Stachura, J;Miettinen, M
胃肠道间质瘤（GIST）是胃肠道常见的间叶性肿瘤。激活KIT或PDGFRA（血小板衍生生长因子受体a）突变已被证明是GIST发病机制的主要力量。最近，以前未描述的N659 K PDGFRA外显子14突变已在GIST中报道。本研究的目的是评估与PDGFRA外显子14突变的GIST的频率，并确定这种肿瘤的临床病理特征。通过PCR扩增和直接测序，对200例KIT外显子9、11、13和17以及PDGFRA外显子12和18突变阴性的GIST进行PDGFRA外显子14突变评估。119例胃GIST中有11例（9%）发现突变。81个胃肠道间质瘤中没有一个有这样的PDGFRA突变。这些突变中的大多数（8例）代表简单的2125 C>A或C>G错义突变，导致赖氨酸取代天冬酰胺（N659 K）。然而，在两个病例中，发现了2123 A>T错义突变，导致酪氨酸取代天冬酰胺（N659 Y）。在11例PDGFRA N659突变型GIST中，10例具有纯上皮样形态。一个肿瘤混合，主要是梭形和局灶性上皮样细胞形态。纯上皮样GIST中PDGFRA N659突变型GIST的频率几乎为19%。免疫组化，这些肿瘤中的大多数（64%）缺乏KIT表达或仅显示局灶性散在KIT阳性。肿瘤大小为2.5 ~ 16 cm（平均7.1 cm）。有丝分裂活性低，
Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumors of the gastrointestinal tract. Activating KIT or PDGFRA (platelet-derived growth factor receptor a) mutations have been shown to be a major force in GIST pathogenesis. Recently, a previously undescribed N659K PDGFRA exon 14 mutation has been reported in GISTs. The purpose of this study was to evaluate the frequency of GISTs with PDGFRA exon 14 mutations and define the clinicopathologic profile of such tumors. In all, 200 GISTs negative for mutations in KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were evaluated for PDGFRA exon 14 mutations by PCR amplification and direct sequencing. Mutations were found in 11 of 119 (9%) gastric GISTs. None of the 81 GISTs from other than gastric location had such a PDGFRA mutation. A majority of these mutations (eight cases) represented simple 2125C>A or C>G missense mutations, leading to substitution of the lysine for asparagine ( N659K). However, in two cases, 2123A>T missense mutations leading to substitution of the tyrosine for asparagine (N659Y) was found instead. Of 11 PDGFRA N659-mutant GISTs, 10 had pure epithelioid morphology. One tumor had mixed, predominantly spindle and focally epithelioid cell morphology. Frequency of PDGFRA N659-mutant GISTs among pure epithelioid GISTs was almost 19%. Immunohistochemically, the majority (64%) of these tumors lacked KIT expression or showed only focal scattered KIT positivity. Tumor size ranged from 2.5 to 16 cm (average 7.1 cm). Low mitotic activity,