“癌症基因组图谱”联合课题组报告了对超过400个“肾透明细胞癌”样本所做的一项基于基因组、DNA甲基化、RNA和蛋白质组定性的综合分析。这些数据显示了PI(3)K/AKT通道中的频发突变,说明该通道也许是一个潜在的治疗目标;同时也显示了与“染色质相关蛋白”中的特定突变有关的一系列外成改变。一个值得注意的发现是进攻性癌症中一个“代谢迁移”(metabolic shift)的存在,后者与肿瘤阶段和严重程度相关。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi:10.1038/nature12222
Comprehensive molecular characterization of clear cell renal cell carcinoma
The Cancer Genome Atlas Research Network
Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.