Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: Identification of candidate amplified and overexpressed genes

Genes Chromosomes and Cancer - Tập 46 Số 4 - Trang 373-384 - 2007
Gopeshwar Narayan1, V Bourdon2, Seeta R. Chaganti2, Hugo Arias‐Pulido3,4, Subhadra V. Nandula1, Pulivarthi H. Rao5, Lutz Gissmann6, Matthias Dürst7, Achim Schneider8, Bhavana Pothuri9, Mahesh Mansukhani1, Katia Basso10, R. S. K. Chaganti2, Vundavalli V. Murty1,10
1Department of Pathology, Columbia University Medical Center, NY 10032
2Cell Biology Program, Memorial Sloan-Kettering Cancer Center, NY 10021
3Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM
4Department of Tumor Molecular Biology, Instituto Nacional de Cancerología, Bogotá, Colombia
5Baylor College of Medicine, Texas Children's Cancer Center, Houston, TX
6Deutsches Krebsforschungszentrum, Im Neuenheiimer Feld 242, Heidelberg, Germany
7Department of Obstetrics and Gynecology, Friedrich Schiller University, Jena, Germany
8Department of Gynecology, Charité Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin, Germany
9Department of Gynecologic Oncology, Columbia University Medical Center, NY 10032
10Institute for Cancer Genetics, Columbia University Medical Center, NY 10032

Tóm tắt

AbstractCervical cancer (CC) cells exhibit complex karyotypic alterations, which is consistent with deregulation of numerous critical genes in its formation and progression. To characterize this karyotypic complexity at the molecular level, we used cDNA array comparative genomic hybridization (aCGH) to analyze 29 CC cases and identified a number of over represented and deleted genes. The aCGH analysis revealed at least 17 recurrent amplicons and six common regions of deletions. These regions contain several known tumor‐associated genes, such as those involved in transcription, apoptosis, cytoskeletal remodeling, ion‐transport, drug metabolism, and immune response. Using the fluorescence in situ hybridization (FISH) approach we demonstrated the presence of high‐level amplifications at the 8q24.3, 11q22.2, and 20q13 regions in CC cell lines. To identify amplification‐associated genes that correspond to focal amplicons, we examined one or more genes in each of the 17 amplicons by Affymetrix U133A expression arrays and semiquantitative reverse‐transcription PCR (RT‐PCR) in 31 CC tumors. This analysis exhibited frequent and robust upregulated expression in CC relative to normal cervix for genes EPHB2 (1p36), CDCA8 (1p34.3), AIM2 (1q22‐23), RFC4, MUC4, and HRASLS (3q27‐29), SKP2 (5p12‐13), CENTD3 (5q31.3), PTK2, RECQL4 (8q24), MMP1 and MMP13 (11q22.2), AKT1 (14q32.3), ABCC3 (17q21‐22), SMARCA4 (19p13.3) LIG1 (19q13.3), UBE2C (20q13.1), SMC1L1 (Xp11), KIF4A (Xq12), TMSNB (Xq22), and CSAG2 (Xq28). Thus, the gene dosage and expression profiles generated here have enabled the identification of focal amplicons characteristic for the CC genome and facilitated the validation of relevant genes in these amplicons. These data, thus, form an important step toward the identification of biologically relevant genes in CC pathogenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2007 Wiley‐Liss, Inc.

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Genes Chromosomes and Cancer

Tập 46 Số 4

373-384

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