英國科學(xué)家發(fā)現(xiàn)了一個與三分之一以上腎癌相關(guān)的缺陷基因，該項發(fā)現(xiàn)被譽為腎癌研究20年來最重要的突破之一,，將幫助研究人員了解腎癌的發(fā)展機理,，并開發(fā)出新的治療手段和早期診斷方法。該項研究成果發(fā)表在最新一期《自然》雜志上,。
PBRM1 體細胞突變
以前的研究發(fā)現(xiàn),，這個被稱為PBRM1的基因與生俱來,，但對某些人來說，該基因會在生命某個階段受到損害,，從而導(dǎo)致癌癥的發(fā)生,。
新研究表明，在大約四成的腎癌患者身上都可發(fā)現(xiàn)變異的PBRM1基因,，這是自VHL變異基因被發(fā)現(xiàn)以來腎癌研究領(lǐng)域最重大的發(fā)現(xiàn),。科學(xué)家認為,，絕大多數(shù)的腎癌都與這兩個基因的變異相關(guān),。該基因是通過基因圖譜法發(fā)現(xiàn)的，研究人員在257個腎細胞癌病例中發(fā)現(xiàn)了88例PBRM1變異基因,。
PBMR1基因可保持某些細胞的結(jié)構(gòu)井然有序,。它的失活可導(dǎo)致“流氓”分子異常生長為癌癥。該基因為何損壞或被關(guān)閉的確切原因至今尚不清楚,，不過,，研究人員希望通過鑒別該基因，在未來將能找到可對腎癌造成致命一擊的治療手段,；或是通過識別與該基因突變相關(guān)的生物標(biāo)記來找到早期診斷方法,。
當(dāng)腎癌表現(xiàn)出某些癥狀時，它是非常致命的,，幾乎沒有什么有效的治愈手段,。英國威爾克姆基金會桑格研究所的安迪·福特里爾博士表示,，PBMR1基因是腎癌研究“拼圖游戲”中的一塊重要拼圖，起到了改變游戲進程的作用,，從而為研發(fā)腎癌治療手段提供了新的靶標(biāo)和方向,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
