Nat Genet:突破!科学家发现相同肿瘤中存在不同遗传复杂性的癌细胞

2017-01-04 不详 生物谷

图片来源:medicalxpress.com 近日,一项刊登于国际杂志Nature Genetics上的研究报告中,来自美国洛杉矶希达-西奈(Cedars-Sinai)医学院的研究人员通过研究在食管肿瘤的组织样本中鉴别出了2000多个基因突变,从而详细阐述了癌症的复杂性,本文研究表明,单一肿瘤的不同区域或许具有多种遗传模式。 研究者指出,本文研究能够帮助解释为何靶向特殊遗传缺陷反而难以有效

图片来源:medicalxpress.com

近日,一项刊登于国际杂志Nature Genetics上的研究报告中,来自美国洛杉矶希达-西奈(Cedars-Sinai)医学院的研究人员通过研究在食管肿瘤的组织样本中鉴别出了2000多个基因突变,从而详细阐述了癌症的复杂性,本文研究表明,单一肿瘤的不同区域或许具有多种遗传模式。

研究者指出,本文研究能够帮助解释为何靶向特殊遗传缺陷反而难以有效治疗癌症,对患者肿瘤进行单一活组织检查的外科医生仅能够解析部分肿瘤的特性和其遗传突变,此外,癌细胞还会不断改变其遗传组成。Dechen Lin博士表示,一个肿瘤并不是单一的疾病,实际上随着时间延续,其在相同患者机体中是许多种疾病,肿瘤中有数百万个肿瘤细胞,其中不同部分又各不相同。

文章中,研究人员对非常难以治疗的食管鳞癌(esophageal squamous cell carcinoma)进行研究,这种疾病能够攻击机体食道,而食道是连接咽喉和胃部的空管结构,据美国癌症协会数据显示,食道癌患者的5年生存率仅为20%。为了绘制出肿瘤突变的一览表,研究者利用了一种高性能的计算机对来自13名患者机体的51份肿瘤样本的遗传数据进行解析,通过进行复杂的算法研究者对肿瘤组织中的基因以及表观遗传特性进行了分析,表观遗传修饰能够开启/关闭癌细胞中基因的表达。

利用上述技术,研究人员在肿瘤样本中鉴别出了2178个遗传突变,其中许多遗传突变都和诱发癌症发生相关的基因直接相关,其中值得注意的是,研究者仅在肿瘤的部分区域中检测到了许多重要的突变,这就表明癌细胞或许存在一定的复杂性,以及利用单一的活组织检查方法或许会对癌症的遗传组成存在错误解释的可能性。

此外研究者还重建了肿瘤的“传记”,阐明了在疾病生命周期中哪些突变是最先出现的;研究者Benjamin Berman说道,本文研究中我们对不同患者之间以及相同患者机体肿瘤的异质性和突变进行了深入研究,也是我们首次以全方位的视角对单一肿瘤中不同区域的表观遗传改变进行研究。

下一步研究者计划将重要的分析技术应用到其它类型癌症的研究中,来深入探究癌症遗传和表观遗传改变的重要性,这或许为后期科学家们开发新型个体化疗法来抵御癌症或药物耐受性提供新的希望。最后研究者Phillip Koeffler博士说道,很多研究证据都表明,肿瘤的异质性是引发癌症患者药物耐受性和疗法失败的主要原因,基于这种情况,解析基因组的多样性和肿瘤的进化或许就能够为科学家们提供新型的靶点来开发个体化的癌症疗法。

原始出处:

Hao JJ, Lin DC, Dinh HQ, Mayakonda A, Jiang YY, Chang C, Jiang Y, Lu CC, Shi ZZ, Xu X, Zhang Y, Cai Y, Wang JW, Zhan QM, Wei WQ, Berman BP, Wang MR, Koeffler HP.Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamouscell carcinoma.Nat Genet. 2016 Dec;48(12):1500-1507. doi: 10.1038/ng.3683.
 

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    2017-03-14 cy0324
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    2017-09-27 仁心济世
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    2017-09-14 liye789132251
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    2017-01-06 yxch36
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