期刊
GENES CHROMOSOMES & CANCER
卷 47, 期 9, 页码 755-765出版社
WILEY
DOI: 10.1002/gcc.20577
关键词
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资金
- NCI NIH HHS [CA095647] Funding Source: Medline
Recurrent karyotypic abnormalities are a characteristic feature of cervical cancer (CC) cells, which may result in deregulated expression of important genes that contribute to tumor initiation and progression. To examine the role of gain of the long arm of chromosome 20 (20q), one of the common chromosomal gains in CC, we evaluated CC at various stages of progression using single nucleotide polymorphism (SNP) array, gene expression profiling, and fluorescence in situ hybridization (FISH) analyses. This analysis revealed copy number increase (CNI) of 20q in > 50% of invasive CC and identified two focal amplicons at 20q 11.2 and 20q 13.13 in a subset of tumors. We further demonstrate that the acquisition of 20q gain occurs at an early stage in CC development and the high-grade squamous intraepithelial lesions (HSIL) that exhibit 20q CNI are associated (P = 0.05) with persistence or progression to invasive cancer. We identified a total of 26 overexpressed genes as consequence of 20q gain (N = 14), as targets of amplicon I (N = 9; two genes also commonly expressed with 20q gain) and amplicon 2 (N = 6; one gene also commonly expressed with 20q gain). These include a number of functionally important genes in cell cycle regulation (E2FI, TPX2, KIF3B, PIGT, and B4GALT5), nuclear function (CSELI), viral replication (PSMA7 and LAMA5), methylation and chromatin remodeling (ASXLI, AHCY, and C20orf2O), and transcription regulation (TCEA2). Our findings implicate a role for these genes in CC tumorigenesis, represent an important step toward the development of clinically significant biomarkers, and form a framework for testing as molecular therapeutic targets. (C) 2008 Wiley-Liss, Inc.
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