Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: Identification of candidate amplified and overexpressed genes Journal Article
| Authors: | Narayan, G.; Bourdon, V.; Chaganti, S.; Arias-Pulido, H.; Nandula, S. V.; Rao, P. H.; Gissmann, L.; Dürst, M.; Schneider, A.; Pothuri, B.; Mansukhani, M.; Basso, K.; Chaganti, R. S. K.; Murty, V. V. |
| Article Title: | Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: Identification of candidate amplified and overexpressed genes |
| Abstract: | 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), ABBCC3 (17q21-22), SMARCA4 (19p13.3) LIG1 (19q13.3), UBE2C (20q13.1), SMCILI (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. |
| Keywords: | controlled study; human tissue; human cell; gene deletion; genetic analysis; gene; gene overexpression; reverse transcription polymerase chain reaction; gene amplification; gene expression; gene expression profiling; genetic association; cancer cell culture; cell line, tumor; gene expression regulation; cancer genetics; gene number; fluorescence in situ hybridization; microarray analysis; oligonucleotide array sequence analysis; gene identification; uterine cervix cancer; amplicon; gene dosage; uterine cervical neoplasms; chromosome analysis; comparative genomic hybridization; chromosome 11q; complementary dna; chromosome 20q; chromosome 8q; akt1 gene; abcc3 gene; aim2 gene; cdca8 gene; centd3 gene; csag2 gene; ephb2 gene; hrasls gene; kif4a gene; lig1 gene; mmp1 gene; mmp13 gene; muc4 gene; ptk2 gene; recql4 gene; rfc4 gene; skp2 gene; smarca4 gene; smcil1 gene; tmsnb gene; ube2c gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 46 |
| Issue: | 4 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2007-04-01 |
| Start Page: | 373 |
| End Page: | 384 |
| Language: | English |
| DOI: | 10.1002/gcc.20418 |
| PUBMED: | 17243165 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 42" - "Export Date: 17 November 2011" - "CODEN: GCCAE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work