英国科学家发现了一个与三分之一以上肾癌相关的缺陷基因，该项发现被誉为肾癌研究20年来最重要的突破之一，将帮助研究人员了解肾癌的发展机理，并开发出新的治疗手段和早期诊断方法。该项研究成果发表在最新一期《自然》杂志上。
PBRM1 体细胞突变
以前的研究发现，这个被称为PBRM1的基因与生俱来，但对某些人来说，该基因会在生命某个阶段受到损害，从而导致癌症的发生。
新研究表明，在大约四成的肾癌患者身上都可发现变异的PBRM1基因，这是自VHL变异基因被发现以来肾癌研究领域最重大的发现。科学家认为，绝大多数的肾癌都与这两个基因的变异相关。该基因是通过基因图谱法发现的，研究人员在257个肾细胞癌病例中发现了88例PBRM1变异基因。
PBMR1基因可保持某些细胞的结构井然有序。它的失活可导致“流氓”分子异常生长为癌症。该基因为何损坏或被关闭的确切原因至今尚不清楚，不过，研究人员希望通过鉴别该基因，在未来将能找到可对肾癌造成致命一击的治疗手段；或是通过识别与该基因突变相关的生物标记来找到早期诊断方法。
当肾癌表现出某些症状时，它是非常致命的，几乎没有什么有效的治愈手段。英国威尔克姆基金会桑格研究所的安迪·福特里尔博士表示，PBMR1基因是肾癌研究“拼图游戏”中的一块重要拼图，起到了改变游戏进程的作用，从而为研发肾癌治疗手段提供了新的靶标和方向。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09639
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
Ignacio Varela,Patrick Tarpey,Keiran Raine,Dachuan Huang,Choon Kiat Ong,Philip Stephens,Helen Davies,David Jones,Meng-Lay Lin,Jon Teague,Graham Bignell,Adam Butler,Juok Cho,Gillian L. Dalgliesh,Danushka Galappaththige,Chris Greenman,Claire Hardy,Mingming Jia,Calli Latimer,King Wai Lau,John Marshall,Stuart McLaren,Andrew Menzies,Laura Mudie,Lucy Stebbings
The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of ~3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A)1, JARID1C (also known as KDM5C) and SETD2 (ref. 2). These genes encode enzymes that demethylate (UTX, JARID1C) or methylate (SETD2) key lysine residues of histone H3. Modification of the methylation state of these lysine residues of histone H3 regulates chromatin structure and is implicated in transcriptional control3. However, together these mutations are present in fewer than 15% of ccRCC, suggesting the existence of additional, currently unidentified cancer genes. Here, we have sequenced the protein coding exome in a series of primary ccRCC and report the identification of the SWI/SNF chromatin remodelling complex gene PBRM1 (ref. 4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology.