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卵巢癌中的19号染色体重排:锌指基因是特别的靶点。

Chromosome 19 rearrangements in ovarian carcinomas: zinc finger genes are particularly targeted.

作者信息

Smebye Marianne L, Sveen Anita, Haugom Lisbeth, Davidson Ben, Tropé Claes G, Lothe Ragnhild A, Heim Sverre, Skotheim Rolf I, Micci Francesca

机构信息

Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.

出版信息

Genes Chromosomes Cancer. 2014 Jul;53(7):558-67. doi: 10.1002/gcc.22166. Epub 2014 Mar 14.

Abstract

Chromosome 19 is frequently rearranged in ovarian carcinomas, but the pathogenetic consequences of this are not clearly understood. We performed microarray gene expression analysis on 12 ovarian carcinomas that carry a rearranged chromosome 19 in their karyotype. These aberrant chromosomes have previously been microdissected and analyzed by array-based CGH. In the current study, we wanted to explore whether the genomic alterations thus detected correlated with changes in gene expression. The microarray gene expression analysis gave information on 407 genes mapping in gained genomic regions on chromosome 19, of which 92 showed association between DNA gain and upregulated expression. Of the genes showing this association, 39 (42%) showed gain in at least two samples. The majority of these 39 genes of interest (n = 24, 62%) encode zinc finger proteins, which otherwise make up only 15% of the approximately 1,400 genes on chromosome 19. The strongest association was found for ZNF223 which was upregulated in samples with genomic gain compared with samples without gain. We suggest that DNA copy number changes brought about by rearrangements of chromosome 19 contribute to ovarian carcinogenesis by leading to upregulation of ZNF223 and other zinc finger genes. © 2014 Wiley Periodicals, Inc.

摘要

19号染色体在卵巢癌中经常发生重排,但其致病后果尚不清楚。我们对12例核型中携带重排19号染色体的卵巢癌进行了微阵列基因表达分析。这些异常染色体此前已通过基于阵列的比较基因组杂交进行显微切割和分析。在本研究中,我们想探讨如此检测到的基因组改变是否与基因表达变化相关。微阵列基因表达分析提供了位于19号染色体获得性基因组区域的407个基因的信息,其中92个基因显示DNA获得与表达上调之间存在关联。在显示这种关联的基因中,39个(42%)在至少两个样本中显示获得。这39个感兴趣的基因中,大多数(n = 24,62%)编码锌指蛋白,而在19号染色体上约1400个基因中,锌指蛋白仅占15%。与无获得的样本相比,在有基因组获得的样本中ZNF223上调最为明显。我们认为,19号染色体重排导致的DNA拷贝数变化通过导致ZNF223和其他锌指基因的上调而促进卵巢癌发生。© 2014威利期刊公司

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