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

Oncogene volume 22, pages 3489–3499 (2003)Cite this article

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.

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Acknowledgements

We thank Dr Thomas C Wright Jr for reviewing the histology and for critical reading of the manuscript. We also thank the gynecologists at INC, Santa Fe de Bogota, Colombia, for specimen collection. This work was supported by the Elaine B Lesser Fund and the Herbert Irving Comprehensive Cancer Center, Columbia University to VVVSM and a grant (2101-04-021-99) from Colciencias, Colombia, to HAP.

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Authors and Affiliations

  1. Department of Pathology, College of Physicians & Surgeons of Columbia University, New York, USA

    Gopeshwar Narayan, Hugo Arias Pulido, Sanjay Koul, Y Albert Yeh, Mahesh Mansukhani & Vundavalli VVS Murty

  2. Institute for Cancer Genetics, College of Physicians & Surgeons of Columbia University, New York, USA

    Gopeshwar Narayan, Sanjay Koul & Vundavalli VVS Murty

  3. Departments of Genetics and Pathology, Instituto Nacional de Cancerología, Santa Fe de Bogotá, Colombia, USA

    Hugo Arias Pulido, Hernan Vargas & Hector Posso

  4. Baylor College of Medicine, Texas Children's Cancer Center, Houston, TX, USA

    Xin-Yan Lu, Charles P Harris & Pulivarthi H Rao

  5. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA

    Mary Beth Terry

  6. Deutsches Krebsforschungszentrum, Angewandte Tumorvirologie Im Neuenheimer Feld 242, Heidelberg, Germany

    Lutz Gissmann

  7. Department of Obstetrics & Gynecology, Friedrich Schiller University, Jena, Germany

    Achim Schneider

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  1. Gopeshwar Narayan
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Correspondence to Vundavalli VVS Murty.

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Narayan, G., Pulido, H., Koul, S. et al. Genetic analysis identifies putative tumor suppressor sites at 2q35–q36.1 and 2q36.3–q37.1 involved in cervical cancer progression. Oncogene 22, 3489–3499 (2003). https://doi.org/10.1038/sj.onc.1206432

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