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Molecular Genetic Analysis of Small Round Cell Sarcomas and its Application for Pathologic Differential Diagnosis

小圆细胞肉瘤的分子遗传学分析及其在病理鉴别诊断中的应用

基本信息

批准号：
11670199
负责人：
NOJIMA Takayuki
金额：
$ 2.24万
依托单位：
Kanazawa Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670199/
关键词：
Small round cell sarcoma Ewing sarcoma Synovial sarcoma EWS gene c-kit gene Malignant soft tissue tumors Gene rearrangements Pathologic diagnosis c-kit 横紋筋肉腫神経芽腫消化管間質腫瘍組織診断 PNET ユーイング肉腫骨肉腫

项目摘要

1) Analysis on the DNA breakpoint junction of EWS/Fli1 in Ewing sarcoma groupWe studied 13 cases of Ewing sarcoma by a molecular biological technique and detected the EWS/Fli1 fusion transcripts in all cases. In four cases of the examined seven, a consensus sequence, 5'-AGAAAARDRR-3' was found near the breakpoints of both genes. And sequences highly homologous to Alu repeats and/or eukaryotic topoisomerase II cleavage site were also located near the breakpoints in most of cases. These suggest that EWS/Fli1 may be specific to Ewing sarcoma group.2) Detection of expression and mutaion of c-kit gene in small round cell tumors C-kit gene encodes a transmembrane receptor kinase which is expressed in the majority of gastrointestinal stromal tumor (GIST) and in most cases of GIST, mutations in exon 11 of c-kit were reported. We examined a juxtamembrane domain mutation of c-kit ; exon 9 to 11 in 26 cases of GIST, eight of rhabdomyosarcoma, one of neuroblastoma, nine of neurogenic tumor, and 9 of leiomyosarcoma by using RT-PCR method. Immunohistochemically, all of GIST showed positivity for c-kit, and mutaions of exon 9-11 were found in 24. Deletion and/or insertion in exon 11 were detected in 20 cases. Although none of non-GIST mesenchymal-tumor group expressed c-kit protein immunohistochemically, 7 cases of rhabdomyosarcomas, one neuroblastoma, 9 neurogenic tumors, and 7 leiomyosarcomas had mutations in exon 9-11 simillar to those of GIST.Furthermore, abnormalities in exon 11 were found in 5 cases, one, 5, and 3, respectively. These findings of the similarity between GIST group and non-GIST mesenchymal-tumor group is suggested to be the same mechanism of carcinogenesis in small round cell tumors.

1)尤文肉瘤EWS/Fli 1基因断裂点连接分析应用分子生物学技术对13例尤文肉瘤进行了EWS/Fli 1融合基因的检测。在所检测的7个中的4个中，在两个基因的断裂点附近发现了共有序列5 '-AGAAAARDRR-3'。与Alu重复序列和/或真核拓扑异构酶II切割位点高度同源的序列也大多位于断裂点附近。这些表明EWS/Fli 1可能对尤文肉瘤组具有特异性。2）小圆细胞肿瘤中c-kit基因表达和突变的检测C-kit基因编码一种跨膜受体激酶，该激酶在大多数胃肠道间质瘤（GIST）中表达，并且在大多数GIST病例中，有报道称c-kit第11号外显子发生突变。应用RT-PCR方法检测了26例GIST、8例横纹肌肉瘤、1例神经母细胞瘤、9例神经源性肿瘤和9例平滑肌肉瘤中c-kit基因第9 ~ 11外显子的跨膜区突变。免疫组化结果显示，所有GIST均为c-kit阳性，24例GIST存在第9-11外显子突变。第11外显子缺失和/或插入20例。非GIST间质肿瘤组c-kit蛋白均不表达，但7例横纹肌肉瘤、1例神经母细胞瘤、9例神经源性肿瘤和7例平滑肌肉瘤的c-kit蛋白在9-11外显子有类似GIST的突变，另外5例、1例、5例和3例在11外显子有异常。GIST组与非GIST间质肿瘤组之间的相似性表明小圆细胞肿瘤的致癌机制相同。