Integrated genomic and transcriptional profiling identifies chromosomal loci with altered gene expression in cervical cancer.

Integrated genomic and transcriptional profiling identifies chromosomal loci with altered gene expression in cervical cancer.
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DOI:
10.1002/gcc.20590
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发表时间:
2008-10
影响因子:
3.7
通讯作者:
Steenbergen, Renske D. M.
Steenbergen, Renske D. M.
中科院分区:
医学2区
文献类型:
--
作者:
Wilting, Saskia M.;de Wilde, Jillian;Meijer, Chris J. L. M.;Berkhof, Johannes;Yi, Yajun;van Wieringen, Wessel N.;Braakhuis, Boudewijn J. M.;Meijer, Gerrit A.;Ylstra, Bauke;Snijders, Peter J. F.;Steenbergen, Renske D. M.

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为了更好地了解宫颈癌中复发性染色体改变的后果,我们整合了10个鳞状细胞癌(SCC),5个腺癌(AdCA)和6个正常对照的全基因组染色体和转录谱。先前的基因组分析显示,染色体臂1 q、3q和20 q的增加以及8 q、10 q、11 q和13 q的丢失在宫颈癌中是常见的。改变的区域跨越了多个兆碱基,并且位于那里的基因表达受到影响的程度仍然不清楚。这些先前染色体分析癌的表达分析产生了83个基因与癌和正常上皮之间的显着差异表达。应用差异基因位点作图(DIGMAP)分析和阵列CGH表达整合工具(ACE-it)确定了基因表达也发生改变的大染色体改变内的热点。1、3和20号染色体长臂的染色体获得导致位于1q32.1-32.2、3q13.32-23、3q26.32-27.3和20q11.21-13.33的基因表达增加,而11q22.3-25的染色体丢失与位于该区域的基因表达减少有关。DTX 3L、PIK 3R 4、ATP 2C 1和SLC 25 A36的过表达均位于3q21.1-23,并通过DIGMAP、ACE-it或两者鉴定,在由12个SCC和13个正常宫颈外样本组成的独立验证样本集中得到证实。总之,综合染色体和转录分析确定了染色体热点在1 q,3q,11 q和20 q与改变基因表达在大的共同改变的染色体区域在宫颈癌。
For a better understanding of the consequences of recurrent chromosomal alterations in cervical carcinomas, we integrated genome-wide chromosomal and transcriptional profiles of 10 squamous cell carcinomas (SCCs), 5 adenocarcinomas (AdCAs) and 6 normal controls. Previous genomic profiling showed that gains at chromosome arms 1q, 3q, and 20q as well as losses at 8q, 10q, 11q, and 13q were common in cervical carcinomas. Altered regions spanned multiple megabases, and the extent to which expression of genes located there is affected remains unclear. Expression analysis of these previously chromosomally profiled carcinomas yielded 83 genes with significantly differential expression between carcinomas and normal epithelium. Application of differential gene locus mapping (DIGMAP) analysis and the array CGH expression integration tool (ACE-it) identified hotspots within large chromosomal alterations in which gene expression was altered as well. Chromosomal gains of the long arms of chromosome 1, 3, and 20 resulted in increased expression of genes located at 1q32.1-32.2, 3q13.32-23, 3q26.32-27.3, and 20q11.21-13.33, whereas a chromosomal loss of 11q22.3-25 was related to decreased expression of genes located in this region. Overexpression of DTX3L, PIK3R4, ATP2C1, and SLC25A36, all located at 3q21.1-23 and identified by DIGMAP, ACE-it or both, was confirmed in an independent validation sample set consisting of 12 SCCs and 13 normal ectocervical samples. In conclusion, integrated chromosomal and transcriptional profiling identified chromosomal hotspots at 1q, 3q, 11q, and 20q with altered gene expression within large commonly altered chromosomal regions in cervical cancer.
DOI: 10.1016/s0002-9440(10)63498-0
发表时间: 2003-10-01
影响因子: 6
作者:
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通讯作者: Ried, T
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发表时间: 2005-10-01
期刊: CANCER RESEARCH
影响因子: 11.2
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DOI: 10.1111/j.1341-8076.2004.00156.x
发表时间: 2004-02-01
影响因子: 1.6
作者:
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通讯作者: Emi, M