Brit J Cancer:睾丸生殖细胞癌发展过程中分子异质性和早期转移克隆选择

2019-02-25 AlexYang MedSci原创

睾丸生殖细胞癌(TGCC)年轻白种人最常见的恶性肿瘤,且起源于一个胚胎干细胞。最近,有研究人员探究了内瘤的异质性,从而阐释从起始到转移的肿瘤进展过程。研究包括了4例治疗抗性非精原细胞瘤(NS)TGCC的42个纯化后样品,包括了原生殖细胞原位瘤变(GCNIS)和转移样品。研究人员利用全基因组和靶向测序对上述样本进行分析,并重建了它们的进化关系。研究发现,内瘤分子异质性与起初认为的原发性肿瘤的组织学演

睾丸生殖细胞癌(TGCC)年轻白种人最常见的恶性肿瘤,且起源于一个胚胎干细胞。最近,有研究人员探究了内瘤的异质性,从而阐释从起始到转移的肿瘤进展过程。

研究包括了4例治疗抗性非精原细胞瘤(NS)TGCC的42个纯化后样品,包括了原生殖细胞原位瘤变(GCNIS)和转移样品。研究人员利用全基因组和靶向测序对上述样本进行分析,并重建了它们的进化关系。研究发现,内瘤分子异质性与起初认为的原发性肿瘤的组织学演变无关。系统治疗后的转移可以在原发癌症中未鉴定到的癌症干细胞中发生。GCNIS主要缺乏原发NS的分子标记并且由不能发展的优势克隆组成。在没有BRCA1和BRCA2基因直接参与的的证据情况下,研究人员观察到了类BRCA变异的特性。

最后,研究人员指出,他们的数据强烈的支持了NS是由全基因组重复起始的假设。主要表现为癌症干细胞前until中染色体拷贝数的改变、少量体细胞变异的积累,甚至在治疗抗性案例中有上述现象。研究人员还指出,当治疗只患有GCNIS疾病或临床明显NS的患者时,这些异质性的观察结果应该在肿瘤发生的所有阶段进行考虑。

原始出处:

Lambert C. J. Dorssers, Ad J. M. Gillis, Hans Stoop et al. Molecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development. Brit J Cancer. 11 Feb 2019.

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    2019-10-18 aids221
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    2019-02-27 zhangph
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