Mutational analysis of Polycomb genes in solid tumours identifies PHC3 amplification as a possible cancer-driving genetic alteration.

Mutational analysis of Polycomb genes in solid tumours identifies PHC3 amplification as a possible cancer-driving genetic alteration.
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DOI:
10.1038/bjc.2013.454
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发表时间:
2013-09-17
影响因子:
8.8
通讯作者:
Helgason CD
Helgason CD
中科院分区:
医学1区
文献类型:
--
作者:
Crea F;Sun L;Pikor L;Frumento P;Lam WL;Helgason CD

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多梳组基因(Polycomb group genes,PcG)是与大多数癌症标志有关的表观遗传效应子。所有PcG的突变状态从未在实体瘤中进行过系统评估。我们进行了多步骤的分析,在医学上可用的数据库和患者样本,以确定体细胞畸变的PcG。来自1000多名癌症患者的数据首次显示,PcG成员PHC 3在三种上皮肿瘤中扩增(比率:8-35%)。肺癌和子宫癌患者的预后较差(P<0.01)。基因扩增与mRNA过表达相关(P<0.01),提示这种畸变的功能作用。PHC 3扩增可能成为上皮肿瘤相关部分的生物标志物和潜在治疗靶点。
Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (P<0.01). Gene amplification correlates with mRNA overexpression (P<0.01), suggesting a functional role of this aberration. PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours.
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