抹掉整個基因簇的大規(guī)?；蜃儺愒诎┌Y中是常見的,，盡管人們對它們是否實際上驅(qū)動著疾病的發(fā)展仍然不清楚。
近日,，刊登在Science上的一項新的研究表明,，這些被稱作半合子局灶性缺失的突變確實會促進細胞的增生，因為其影響的基因組區(qū)域富集著腫瘤抑制性基因,。人類的腫瘤充斥著重組,、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重大的挑戰(zhàn),。半合子局灶性缺失——它首先會影響某些染色體區(qū)域并導致一整組相鄰基因的一個拷貝的喪失——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性屬性的基因,。他們發(fā)現(xiàn)了多個對增生進行負面或正面調(diào)節(jié)的“停止”和“開動”基因,。半合子局灶性缺失似乎所針對的是具有相對多數(shù)的“停止”基因及相對少數(shù)的“開動”基因的“基因島”。Solimini及其同事提出了一個“基因島假說”,，該假說提示,，有這些缺失的細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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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.
