Genetic analysis identifies putative tumor suppressor sites at 2q35-q36.1 and 2q36.3-q37.1 involved in cervical cancer progression

Gopeshwar Narayan, Hugo Arias Pulido, Sanjay Koul, Xin Yan Lu, Charles P. Harris, Y. Albert Yeh, Hernan Vargas, Hector Posso, Mary Beth Terry, Lutz Gissmann, Achim Schneider, Mahesh Mansukhani, Pulivarthi H. Rao, Vundavalli V V S Murty

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

We performed comparative genomic hybridization (CGH) and high-resolution deletion mapping of the long arm of chromosome 2 (2q) in invasive cervical carcinoma (CC). The CGH analyses on 52 CCs identified genetic losses at 2q33-q36, gain of 3q26-q29, and frequent chromosomal amplifications. Characterization of 2q deletions by loss of heterozygosity (LOH) in 60 primary tumors identified two sites of minimal deleted regions at 2q35-q36.1 and 2q36.3-q37.1. To delineate the stage at which these genetic alterations occur in CC progression, we analysed 33 cervical intraepithelial neoplasia (CIN) for LOH. We found that 89% of high-grade (CINII and CINIII) and 40% of low-grade (CINI) CINs exhibited LOH at 2q. To identify the target tumor suppressor gene (TSG), we performed an extensive genetic and epigenetic analyses of a number of candidate genes mapped to the deleted regions. We did not find inactivating mutations in CASP10, BARD1, XRCC5, or PPP1R7 genes mapped to the deleted regions. However, we did find evidence of downregulated gene expression in CFLAR, CASP10 and PPP1R7 in CC cell lines. We also found reactivated gene expression in CC cell lines in vitro after exposure to demethylating and histone deacetylase (HDAC) inhibiting agents. Thus, these data identify frequent chromosomal amplifications in CC, and sites of TSGs at 2q35-q36.1 and 2q36.3-q37.1 that are critical in CC development.

Original languageEnglish (US)
Pages (from-to)3489-3499
Number of pages11
JournalOncogene
Volume22
Issue number22
DOIs
StatePublished - May 29 2003

Keywords

  • CGH
  • Cervical carcinoma
  • Cervical intraepithelial neoplasia
  • Chromosome 2
  • Gene amplification
  • LOH

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Narayan, G., Pulido, H. A., Koul, S., Lu, X. Y., Harris, C. P., Yeh, Y. A., Vargas, H., Posso, H., Terry, M. B., Gissmann, L., Schneider, A., Mansukhani, M., Rao, P. H., & Murty, V. V. V. S. (2003). Genetic analysis identifies putative tumor suppressor sites at 2q35-q36.1 and 2q36.3-q37.1 involved in cervical cancer progression. Oncogene, 22(22), 3489-3499. https://doi.org/10.1038/sj.onc.1206432