...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Genes, Chromosomes and Cancer >Overexpression of insulin-like growth factor 1 receptor and frequent mutational inactivation of SDHA in wild-type SDHB-negative gastrointestinal stromal tumors
【24h】

Overexpression of insulin-like growth factor 1 receptor and frequent mutational inactivation of SDHA in wild-type SDHB-negative gastrointestinal stromal tumors

机译：野生型SDHB阴性胃肠道间质瘤中胰岛素样生长因子1受体的过表达和SDHA的频繁突变失活

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Approximately 15% of gastrointestinal stromal tumors (GISTs) in adults and 85% in children lack mutations in KIT and PDGFRA and are known as wild-type GISTs. Wild-type GISTs from adults and children express high levels of insulin-like growth factor 1 receptor (IGF1R) and exhibit stable genomes compared to mutant GISTs. Pediatric wild-type GISTs, GISTs from the multitumor Carney-Stratakis syndrome, and the Carney triad share other clinicopathological properties (e.g., early-onset, multifocal GISTs with epitheliod cell morphology), suggesting a common etiology. Carney-Stratakis is an inherited association of GIST and paragangliomas caused by germline mutations in succinate dehydrogenase (SDH) genes. The connection between defective cellular respiration and GIST pathology has been strengthened by the utilization of SDHB immunohistochemistry to identify SDH deficiency in pediatric GISTs, syndromic GISTs, and some adult wild-type GISTs. SDHB and IGF1R expression was examined in 12 wild-type and 12 mutant GIST cases. Wild-type GISTs were screened for coding-region alterations in SDH genes and for chromosomal aberrations using genome-wide single-nucleotide polymorphism and MIP arrays. SDHB-deficiency, identified in 11/12 wild-type GIST cases, was tightly associated with overexpression of IGF1R protein and transcript. Biallelic inactivation of the SDHA gene was a surprisingly frequent event, identified in 5 of 11 SDHB-negative cases, generally due to germline point mutations accompanied by somatic SDHA allelic losses. As a novel finding, inactivation of the SDHC gene from a combination of a heterozygous coding-region mutation and hypermethylation of the wild-type allele was found in one SDHB-negative case.
机译：成人中大约15％的胃肠道间质瘤（GIST）和儿童中的85％没有KIT和PDGFRA突变，被称为野生型GIST。与突变型GIST相比，来自成人和儿童的野生型GIST表达高水平的胰岛素样生长因子1受体（IGF1R）并显示稳定的基因组。小儿野生型GIST，来自多肿瘤Carney-Stratakis综合征的GIST和Carney三元组具有其他临床病理特征（例如，具有上皮细胞形态的早发多灶GIST），这提示了常见的病因。 Carney-Stratakis是由琥珀酸脱氢酶（SDH）基因的种系突变引起的GIST和副神经节瘤的遗传关联。通过利用SDHB免疫组织化学来鉴定小儿GIST，综合征性GIST和某些成年野生型GIST中的SDH缺陷，已加强了细胞呼吸不良与GIST病理之间的联系。在12个野生型和12个突变GIST病例中检查了SDHB和IGF1R表达。使用全基因组范围的单核苷酸多态性和MIP阵列，筛选野生型GIST的SDH基因编码区变化和染色体畸变。在11/12野生型GIST病例中发现的SDHB缺乏症与IGF1R蛋白和转录物的过表达密切相关。 SDHA基因的双等位基因失活是一个出乎意料的频繁事件，在11个SDHB阴性病例中有5个被发现，通常是由于种系点突变伴随体细胞SDHA等位基因缺失所致。作为一项新发现，在一个SDHB阴性病例中，发现杂合的编码区突变和野生型等位基因的高甲基化使SDHC基因失活。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号