Nature:中国科学家发现食管鳞癌相关基因突变
华大基因 · 2014/03/17
来自中国医学科学院肿瘤医院分子肿瘤学国家重点实验室等多家单位的科研人员通过高通量测序、比较基因组杂交芯片分析及生物学功能研究,全面系统揭示了食管鳞癌的遗传突变背景,为了解食管鳞癌的发病机理、诊断的分子标志物,提供了理论和实验依据。


2014年3月17日,来自中国医学科学院肿瘤医院分子肿瘤学国家重点实验室、华大基因、汕头大学医学院等多家单位的科研人员通过高通量测序、比较基因组杂交芯片分析及生物学功能研究,全面系统揭示了食管鳞癌的遗传突变背景,发现了一批与食管鳞癌发生发展进程和临床预后相关的基因,为了解食管鳞癌的发病机理,寻找食管鳞癌诊断的分子标志物,确定研发临床治疗的药物靶点以及制定有效的治疗方案提供了理论和实验依据。最新研究成果于国际学术权威杂志《自然》(Nature)在线发表。

食管癌是人类常见的恶性肿瘤之一,在我国和全球所有恶性肿瘤死亡率中分别排在第四位和第六位。令人关注是,我国食管癌发病率和死亡率均居世界首位。最新统计数据显示,2012年食管癌新发病例达45.6万例,病理分型主要为鳞癌。食管癌病程进展快,预后差,五年生存率仅为10%左右。目前,食管癌发生和发展的机制尚不明了,治疗缺乏特异性的分子靶点和有效的治疗药物。

在本研究中,科研人员对我国食管鳞癌患者样本进行了全基因组测序、全外显子组测序和比较基因组杂交芯片分析,发现了8个与食管鳞癌发生相关的重要的基因突变,其中FAM135B是首次发现的肿瘤相关基因;同时获得了食管鳞癌拷贝数变异的重要数据,发现位于染色体11q13.3-13.4扩增区域的MIR548K参与食管鳞癌的恶性表型的形成。

该项研究还发现,重要组蛋白调节基因MLL2、ASH1L、MLL3、SETD1B和CREBBP/EP300在食管鳞癌中呈现频繁非沉默突变;对潜在治疗靶点进行分析,发现PI3K是食管鳞癌突变频率最高的潜在药靶,以及PSMD2、RARRES1、SRC、GSK3β和SGK3等潜在新药靶。研究人员整合了所有基因突变和基因拷贝变异数据,确定了与食管鳞癌发生发展相关的重要信号通路,包括Wnt、cell cycle、Notch、RTK-Ras和AKT通路。

该项目负责人,中国医学科学院肿瘤医院分子肿瘤学国家重点实验室主任詹启敏教授谈到:“这个研究项目的科学发现对于我们理解食管鳞癌的发病机制有极大的帮助,可以帮助我们寻找食管癌的诊断标志物、药物靶点和制定临床治疗方案。更有意义的是,食管癌是中国的高发特色肿瘤,提高食管癌的诊疗能力是中国科学家的责任。另外,我们很高兴看到,这项工作是通过国内多家优势单位协同创新取得的成果。”

华大基因该项目负责人李林提到:“在该项研究中,我们描绘了食管鳞癌基因组变异谱,发现了食管鳞癌重要的突变基因及通路,为研究食管鳞癌的发生发展机制提供了更全面的指导,为食管鳞癌分子分型,药物研发及个性化治疗方法提供了科学基础,加快了食管癌研究进程。”

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