抹掉整個(gè)基因簇的大規(guī)?；蜃儺愒诎┌Y中是常見(jiàn)的,，盡管人們對(duì)它們是否實(shí)際上驅(qū)動(dòng)著疾病的發(fā)展仍然不清楚。
近日,，刊登在Science上的一項(xiàng)新的研究表明，這些被稱(chēng)作半合子局灶性缺失的突變確實(shí)會(huì)促進(jìn)細(xì)胞的增生,，因?yàn)槠溆绊懙幕蚪M區(qū)域富集著腫瘤抑制性基因,。人類(lèi)的腫瘤充斥著重組、清除,、放大或以其他方式破壞一系列基因的基因組改變,。確定在這許多改變中有哪些在癌癥中起著致病性的作用是一個(gè)重大的挑戰(zhàn)。半合子局灶性缺失——它首先會(huì)影響某些染色體區(qū)域并導(dǎo)致一整組相鄰基因的一個(gè)拷貝的喪失——尤其令人困惑,。
Nicole Solimini及其同事在這些缺失中尋找具有癌癥相關(guān)性屬性的基因。他們發(fā)現(xiàn)了多個(gè)對(duì)增生進(jìn)行負(fù)面或正面調(diào)節(jié)的“停止”和“開(kāi)動(dòng)”基因,。半合子局灶性缺失似乎所針對(duì)的是具有相對(duì)多數(shù)的“停止”基因及相對(duì)少數(shù)的“開(kāi)動(dòng)”基因的“基因島”。Solimini及其同事提出了一個(gè)“基因島假說(shuō)”,，該假說(shuō)提示，有這些缺失的細(xì)胞也許更有可能增生并產(chǎn)生腫瘤,。（生物谷Bioon.com）
doi:10.1126/science.1219580
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PMID:
Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential
Nicole L. Solimini1, Qikai Xu1, Craig H. Mermel2,3, Anthony C. Liang1, Michael R. Schlabach1,*, Ji Luo1,†, Anna E. Burrows1, Anthony N. Anselmo1, Andrea L. Bredemeyer1, Mamie Z. Li1, Rameen Beroukhim2,3,4, Matthew Meyerson2,3, Stephen J. Elledge1,‡
Tumors exhibit numerous recurrent hemizygous focal deletions that contain no known tumor suppressors and are poorly understood. To investigate whether these regions contribute to tumorigenesis, we searched genetically for genes with cancer-relevant properties within these hemizygous deletions. We identified STOP and GO genes, which negatively and positively regulate proliferation, respectively. STOP genes include many known tumor suppressors, while GO genes are enriched for essential genes. Analysis of their chromosomal distribution revealed that recurring deletions preferentially over-represent STOP genes and under-represent GO genes. We propose a hypothesis called the Cancer Gene Island model whereby gene islands encompassing high densities of STOP genes and low densities of GO genes are hemizygously deleted to maximize proliferative fitness through cumulative haploinsufficiencies. Since thousands of genes are hemizygously deleted per tumor, this mechanism may help drive tumorigenesis.
