“癌癥基因組圖譜”聯(lián)合課題組報(bào)告了對(duì)超過(guò)400個(gè)“腎透明細(xì)胞癌”樣本所做的一項(xiàng)基于基因組,、DNA甲基化、RNA和蛋白質(zhì)組定性的綜合分析,。這些數(shù)據(jù)顯示了PI(3)K/AKT通道中的頻發(fā)突變,，說(shuō)明該通道也許是一個(gè)潛在的治療目標(biāo)；同時(shí)也顯示了與“染色質(zhì)相關(guān)蛋白”中的特定突變有關(guān)的一系列外成改變,。一個(gè)值得注意的發(fā)現(xiàn)是進(jìn)攻性癌癥中一個(gè)“代謝遷移”（metabolic shift）的存在，后者與腫瘤階段和嚴(yán)重程度相關(guān),。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
