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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >microRNAs exhibit high frequency genomic alterations in human cancer
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microRNAs exhibit high frequency genomic alterations in human cancer

机译：microRNA在人类癌症中表现出高频基因组改变

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摘要

MicroRNAs (miRNAs) are endogenous noncoding RNAs, which negatively regulate gene expression. To determine genomewide miRNA DNA copy number abnormalities in cancer, 283 known human miRNA genes were analyzed by high-resolution array-based comparative genomic hybridization in 227 human ovarian cancer, breast cancer, and melanoma specimens. A high proportion of genomic loci containing miRNA genes exhibited DNA copy number alterations in ovarian cancer (37.1%), breast cancer (72.8%), and melanoma (85.9%), where copy number alterations observed in > 15% tumors were considered significant for each miRNA gene. We identified 41 miRNA genes with gene copy number changes that were shared among the three cancer types (26 with gains and 15 with losses) as well as miRNA genes with copy number changes that were unique to each tumor type. Importantly, we show that miRNA copy changes correlate with miRNA expression. Finally, we identified high frequency copy number abnormalities of Dicer1, Argonaute2, and other miRNA-associated genes in breast and ovarian cancer as well as melanoma. These findings support the notion that copy number alterations of miRNAs and their regulatory genes are highly prevalent in cancer and may account partly for the frequent miRNA gene deregulation reported in several tumor types.
机译：微小RNA（miRNA）是内源性非编码RNA，会对基因表达产生负调控。为了确定癌症中的全基因组miRNA DNA拷贝数异常，通过基于高分辨率阵列的比较基因组杂交分析了227个人类卵巢癌，乳腺癌和黑色素瘤样本中的283个已知人类miRNA基因。包含miRNA基因的基因组基因座中，有很大一部分在卵巢癌（37.1％），乳腺癌（72.8％）和黑素瘤（85.9％）中表现出DNA拷贝数改变，其中在> 15％的肿瘤中观察到的拷贝数改变被认为具有重要意义。每个miRNA基因。我们鉴定了41种miRNA基因，其基因拷贝数变化在三种癌症类型中（共有26种有增加，而15种有丢失）在每种肿瘤类型中均具有相同的拷贝数变化。重要的是，我们表明miRNA复制变化与miRNA表达相关。最后，我们在乳腺癌和卵巢癌以及黑色素瘤中发现了Dicer1，Argonaute2和其他miRNA相关基因的高频拷贝数异常。这些发现支持以下观点：miRNA及其调节基因的拷贝数改变在癌症中非常普遍，并且可能部分解释了几种肿瘤类型中频繁报道的miRNA基因失调。

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