PMID- 17243165 OWN - NLM STAT- MEDLINE DCOM- 20070418 LR - 20220409 IS - 1045-2257 (Print) IS - 1045-2257 (Linking) VI - 46 IP - 4 DP - 2007 Apr TI - Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. PG - 373-84 AB - Cervical 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. CI - (c) 2007 Wiley-Liss, Inc. FAU - Narayan, Gopeshwar AU - Narayan G AD - Department of Pathology, Columbia University Medical Center, NY 10032, USA. FAU - Bourdon, Veronique AU - Bourdon V FAU - Chaganti, Seeta AU - Chaganti S FAU - Arias-Pulido, Hugo AU - Arias-Pulido H FAU - Nandula, Subhadra V AU - Nandula SV FAU - Rao, Pulivarthi H AU - Rao PH FAU - Gissmann, Lutz AU - Gissmann L FAU - Durst, Matthias AU - Durst M FAU - Schneider, Achim AU - Schneider A FAU - Pothuri, Bhavana AU - Pothuri B FAU - Mansukhani, Mahesh AU - Mansukhani M FAU - Basso, Katia AU - Basso K FAU - Chaganti, R S K AU - Chaganti RS FAU - Murty, Vundavalli V AU - Murty VV LA - eng GR - CA095647/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 SB - IM MH - Cell Line, Tumor MH - Female MH - *Gene Amplification MH - *Gene Dosage MH - *Gene Expression MH - Humans MH - *Oligonucleotide Array Sequence Analysis MH - Uterine Cervical Neoplasms/*genetics EDAT- 2007/01/24 09:00 MHDA- 2007/04/19 09:00 CRDT- 2007/01/24 09:00 PHST- 2007/01/24 09:00 [pubmed] PHST- 2007/04/19 09:00 [medline] PHST- 2007/01/24 09:00 [entrez] AID - 10.1002/gcc.20418 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 2007 Apr;46(4):373-84. doi: 10.1002/gcc.20418.