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Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: Potential role in progression
Author(s) -
Scotto Luigi,
Narayan Gopeshwar,
Nandula Subhadra V.,
AriasPulido Hugo,
Subramaniyam Shivakumar,
Schneider Achim,
Kaufmann Andreas M.,
Wright Jason D.,
Pothuri Bhavana,
Mansukhani Mahesh,
Murty Vundavalli V.
Publication year - 2008
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20577
Subject(s) - biology , amplicon , carcinogenesis , pax5 , tumor progression , cancer research , gene , single nucleotide polymorphism , genetics , fluorescence in situ hybridization , comparative genomic hybridization , copy number variation , gene duplication , chromosome , transcription factor , genome , genotype , polymerase chain reaction
Abstract 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 20q11.2 and 20q13.13 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 1 ( 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 ( E2F1 , TPX2 , KIF3B , PIGT , and B4GALT5 ), nuclear function ( CSEL1 ), viral replication ( PSMA7 and LAMA5 ), methylation and chromatin remodeling ( ASXL1 , AHCY , and C20orf20 ), 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. © 2008 Wiley‐Liss, Inc.