科學(xué)家們已經(jīng)確定出新乳腺癌基因，它們能改變疾病診斷方法,，構(gòu)成新一代治療方法的基礎(chǔ),。這些科學(xué)家來(lái)自加拿大BC癌癥研究機(jī)構(gòu)和英國(guó)哥倫比亞大學(xué)。這是目前開(kāi)展過(guò)的最大規(guī)模的全球性乳腺癌組織的研究,，科學(xué)家對(duì)2000份腫塊樣本進(jìn)行了DNA和RNA分析,，這些樣本取自5至10年前被診斷為乳腺癌的女性，可謂達(dá)到了該疾病數(shù)十年研究的最高點(diǎn),。相關(guān)研究結(jié)果發(fā)表在Nature上,。
研究人員根據(jù)腫塊的遺傳指紋圖譜，已將乳腺癌重新分類,，分成10個(gè)全新類別。許多這些基因能提供乳腺癌生物學(xué)的急需見(jiàn)解,，使醫(yī)生能對(duì)如下情況作出預(yù)測(cè)：腫塊是否對(duì)特定治療方法響應(yīng),，是否可能擴(kuò)散到身體其他部位,，或是否可能隨著治療而復(fù)發(fā)。這個(gè)信息將來(lái)可被醫(yī)生用于更好地制定個(gè)體化治療方案,。其里程碑意義表現(xiàn)在：
用存活關(guān)聯(lián)的普通遺傳特征將乳腺癌劃分為10個(gè)亞型,。這種新分類可能改變制定乳腺癌女性藥物治療的方法。
發(fā)現(xiàn)幾個(gè)以前與乳腺無(wú)關(guān)聯(lián)的全新基因,。這些驅(qū)動(dòng)疾病的基因是新藥物的靶標(biāo),。該信息可被全球科學(xué)家用來(lái)推進(jìn)藥物發(fā)現(xiàn)與開(kāi)發(fā)。
揭示了這些基因與已知細(xì)胞信號(hào)通路之間的關(guān)系,，其中已知細(xì)胞信號(hào)通路就是控制細(xì)胞生長(zhǎng)與分化的網(wǎng)狀系統(tǒng),。通過(guò)破壞重要的細(xì)胞過(guò)程，它能指明這些基因故障如何引起癌癥,。
它是BC癌癥研究機(jī)構(gòu)這幾周內(nèi)宣布的第二個(gè)重大突破,。4月4日，Sam Aparicio博士領(lǐng)導(dǎo)一個(gè)研究團(tuán)隊(duì)剛剛慶祝了解碼三陰性乳腺癌基因構(gòu)成,，這是一種致命性最強(qiáng)的乳腺癌,。類似于那個(gè)公告，今天的新發(fā)現(xiàn)鑒定了一些基因,，它們是先前未知的,、與乳腺癌相關(guān)的基因，并清楚地指出乳腺癌真正是一個(gè)大量獨(dú)特疾病的總稱,。
盡管該研究不可能使當(dāng)前患病的女性受益,，但它大大推動(dòng)了科學(xué)家們?nèi)绾螌?shí)現(xiàn)深入研究和臨床試驗(yàn)，為他們提供了一個(gè)開(kāi)發(fā)新治療方案和針對(duì)特定基因藥物的跳板,。（生物谷bioon.com）
doi:10.1038/nature10983
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The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
Christina Curtis, Sohrab P. Shah, Suet-Feung Chin, Gulisa Turashvili, Oscar M. Rueda, Mark J. Dunning, Doug Speed, Andy G. Lynch, Shamith Samarajiwa, Yinyin Yuan, Stefan Gr?f, Gavin Ha,Gholamreza Haffari, Ali Bashashati, Roslin Russell, Steven McKinney, METABRIC Group, Anita Langer?d, Andrew Green, Elena Provenzano, Gordon Wishart, Sarah Pinder, Peter Watson,Florian Markowetz, Leigh Murphy et al.
The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA-RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the 'CNA-devoid' subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome.
