我國(guó)科學(xué)家研究指出,，染色質(zhì)重塑異常可能是導(dǎo)致膀胱癌發(fā)生的一個(gè)重要標(biāo)志,。近日,，由北京大學(xué)深圳醫(yī)院和深圳華大基因主導(dǎo)完成的研究成果——“膀胱移行細(xì)胞癌中染色質(zhì)重塑相關(guān)基因突變的研究”在國(guó)際著名雜志《自然—遺傳學(xué)》上在線發(fā)表。此研究成果為膀胱癌的診斷,、治療奠定了堅(jiān)實(shí)的遺傳學(xué)基礎(chǔ),。
膀胱移行細(xì)胞癌是膀胱癌中最常見的組織學(xué)類型，男性發(fā)病率約為女性的3—4倍,，多發(fā)生于40—70歲之間,。
染色質(zhì)重塑是表觀遺傳修飾模式中的一種重要機(jī)制，其中的任何一個(gè)環(huán)節(jié)發(fā)生異常都會(huì)影響基因的正常表達(dá),，從而引起很多復(fù)雜的疾病,。如果突變引起抑癌基因或調(diào)節(jié)細(xì)胞周期的蛋白出現(xiàn)異常，則可能會(huì)導(dǎo)致癌癥的發(fā)生和發(fā)展,，所以研究人員對(duì)膀胱移行細(xì)胞癌中染色質(zhì)重塑相關(guān)基因進(jìn)行了研究,。研究發(fā)現(xiàn)了8個(gè)與染色質(zhì)重塑相關(guān)的突變基因，除了UTX基因外,，其他7個(gè)突變基因在原發(fā)性膀胱移行細(xì)胞癌中是首次被發(fā)現(xiàn),。在97例膀胱移行細(xì)胞癌患者樣本中，有59%的患者的染色質(zhì)重塑相關(guān)基因發(fā)生了體細(xì)胞突變,，由此研究人員推測(cè)染色質(zhì)重塑異?？赡苁菍?dǎo)致膀胱移行細(xì)胞癌發(fā)生及發(fā)展的重要機(jī)制之一，這為目前難以醫(yī)治的腫瘤提供了新的分子靶點(diǎn),。
北京大學(xué)深圳醫(yī)院桂耀庭博士介紹,，國(guó)內(nèi)外還未曾對(duì)膀胱移行細(xì)胞癌進(jìn)行系統(tǒng)、全面的基因組學(xué)分析,。他們希望通過本次研究,，發(fā)現(xiàn)一些與膀胱癌相關(guān)的新基因，為該病的診斷,、治療提供更多有價(jià)值的信息,。在本研究中，他們對(duì)9例TCC患者樣本進(jìn)行了外顯子測(cè)序研究,，并在88例TCC患者樣本中進(jìn)行驗(yàn)證,，發(fā)現(xiàn)54個(gè)與TCC發(fā)生相關(guān)的顯著突變基因，其中49個(gè)基因是首次在膀胱癌中被發(fā)現(xiàn),。(生物谷 Bioon.com)
doi:10.1038/ng.907
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Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder
Yaoting Gui; Guangwu Guo; Yi Huang; Xueda Hu; Aifa Tang; Shengjie Gao; Renhua Wu; Chao Chen; Xianxin Li; Liang Zhou; Minghui He; Zesong Li; Xiaojuan Sun; Wenlong Jia; Jinnong Chen; Shangming Yang; Fangjian Zhou; Xiaokun Zhao; Shengqing Wan; Rui Ye; Chaozhao Liang; Zhisheng Liu; Peide Huang; Chunxiao Liu; Hui Jiang; Yong Wang; Hancheng Zheng; Liang Sun; Xingwang Liu; Zhimao Jiang; Dafei Feng; Jing Chen; Song Wu; Jing Zou; Zhongfu Zhang; Ruilin Yang; Jun Zhao; Congjie Xu; Weihua Yin; Zhichen Guan;
Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.
