Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Export

@article{citeulike:3081686, 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.}, address = {Department of Pathology, Columbia University Medical Center, New York, NY; Department of Tumor Molecular Biology, Instituto Nacional de Cancerolog\'{\i}a, Bogot\'{a}, Colombia; Division of Hematology/Oncology, The University of New Mexico Cancer Center, Albuquerque, NM; Department of Gynecology, Charit\'{e} Universit\"{a}tsmedizin Berlin, Hindenburgdamm 30, Berlin, Germany; Department of Gynecologic Oncology, Columbia University Medical Center, New York, NY; Institute for Cancer Genetics, Columbia University Medical Center, New York, NY}, author = {Scotto, Luigi and Narayan, Gopeshwar and Nandula, Subhadra V. and Arias-Pulido, Hugo and Subramaniyam, Shivakumar and Schneider, Achim and Kaufmann, Andreas M. and Wright, Jason D. and Pothuri, Bhavana and Mansukhani, Mahesh and Murty, Vundavalli V.}, citeulike-article-id = {3081686}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/gcc.20577}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18506748}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18506748}, citeulike-linkout-3 = {http://www3.interscience.wiley.com/cgi-bin/abstract/119427752/ABSTRACT}, doi = {10.1002/gcc.20577}, issn = {1098-2264}, journal = {Genes, chromosomes \& cancer}, keywords = {20q, cervical\_cancer, copy-number, gene\_expression, integration}, month = {September}, number = {9}, pages = {755--765}, posted-at = {2009-11-02 16:58:49}, priority = {0}, title = {Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression.}, url = {http://dx.doi.org/10.1002/gcc.20577}, volume = {47}, year = {2008} }

TY - JOUR ID - citeulike:3081686 L3 - citeulike-article-id:3081686 N2 - 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. IS - 9 JF - Genes, chromosomes & cancer SN - 1098-2264 AD - Department of Pathology, Columbia University Medical Center, New York, NY; Department of Tumor Molecular Biology, Instituto Nacional de Cancerología, Bogotá, Colombia; Division of Hematology/Oncology, The University of New Mexico Cancer Center, Albuquerque, NM; Department of Gynecology, Charité Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin, Germany; Department of Gynecologic Oncology, Columbia University Medical Center, New York, NY; Institute for Cancer Genetics, Columbia University Medical Center, New York, NY EP - 765 TI - Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. VL - 47 SP - 755 KW - 20q KW - cervical_cancer KW - copy-number KW - gene_expression KW - integration AU - Scotto, Luigi AU - Narayan, Gopeshwar AU - Nandula, Subhadra AU - Arias-Pulido, Hugo AU - Subramaniyam, Shivakumar AU - Schneider, Achim AU - Kaufmann, Andreas AU - Wright, Jason AU - Pothuri, Bhavana AU - Mansukhani, Mahesh AU - Murty, Vundavalli PY - 2008/09// UR - http://dx.doi.org/10.1002/gcc.20577 ER -