Mapping common deleted regions on 5p15 in cervical carcinoma and their occurrence in precancerous lesions

Arias-Pulido Hugo, Narayan Gopeshwar, Vargas Hernan, Mansukhani Mahesh, Murty

Description

Previous studies have shown that the short arm of chromosome 5 (5p) exhibit frequent genetic changes in invasive cervical carcinoma (CC), and that these changes arise early during the carcinogenesis, in precancerous lesions. These data therefore suggest that loss of candidate tumor suppressor genes located on 5p is associated with the development of CC. However, the precise location of 5p deletions is not known. Results We performed a detailed deletion mapping of 5p in 60 cases of invasive CC. We found that 60% of the tumors exhibit a 5p loss of heterozygosity (LOH). The patterns of LOH allowed us to identify two minimal regions of deletions, one at 5p15.3 spanning a 5.5 cM genetic distance and a second site of 7 cM at 5p15.2-15.3. In addition, we also identified 5p deletions in 16% lesions of high-grade cervical intraepithelial neoplasia (CIN). 5p LOH was found in 63% of HPV 16 positive tumors, while only 33% tumors with other HPV-types had 5p LOH. The differences in frequency of 5p LOH between tumors harboring HPV16 in combination with other HPV types and tumors harboring HPV16 DNA alone were significantly higher, suggesting a synergistic effect of high-risk types in causing genomic instability. Conclusion These findings implicate the presence of tumor suppressor gene(s) on 5p relevant to CC tumorigenesis.

Sujets

• Cervical cancer
• Cervical intraepithelial neoplasia
• Loss of heterozygosity
• Deletion mapping
• Human papillomavirus

Informations

• Publié par: biomed
• Publié le: 01 janvier 2002
• Nombre de lectures: 9
• Langue: English

Extrait

Molecular Cancer

BioMedCentral

M20o0le2c,ular Cancerx 1 Open Access Research Mapping common deleted regions on 5p15 in cervical carcinoma and their occurrence in precancerous lesions 1,3,4 13 Hugo AriasPulido, Gopeshwar Narayan, Hernan Vargas, 1 1,2 Mahesh Mansukhaniand Vundavalli VVS Murty*

1 Address: Departmentof Pathology, College of Physicians & Surgeons of Columbia University, 630 West 168th Street, New York, 10032, USA, 2 Institute for Cancer Genetics, College of Physicians & Surgeons of Columbia University, 630 West 168th Street, New York, 10032, USA, 3 4 Department of Tumor Molecular Biology, Instituto Nacional de Cancerología, Cl. 1 No 985, Bogotá, Colombia andDepartment of Molecular Genetics and Microbiology, BRF 123, School of Medicine, 915 Camino de Salud, NE., Albuquerque, NM, 87131, USA Email: Hugo AriasPulido  [e-mail]; Gopeshwar Narayan  [e-mail]; Hernan Vargas  [e-mail]; Mahesh Mansukhani  [e-mail]; Vundavalli VVS Murty*  [e-mail] *Corresponding author

Published: 1 October 2002Received: 26 September 2002 Accepted: 1 October 2002 Molecular Cancer2002,1:3 This article is available from: http://www.molecular-cancer.com/content/1/1/3 © 2002 Arias-Pulido et al; licensee BioMed Central Ltd. This article is published in Open Access: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

Keywords:Cervical carcinoma, cervical intraepithelial neoplasia, chromosome 5p, loss of heterozygosity, deletion mapping, human papilloma virus

Abstract Background:Previous studies have shown that the short arm of chromosome 5 (5p) exhibit frequent genetic changes in invasive cervical carcinoma (CC), and that these changes arise early during the carcinogenesis, in precancerous lesions. These data therefore suggest that loss of candidate tumor suppressor genes located on 5p is associated with the development of CC. However, the precise location of 5p deletions is not known. Results:We performed a detailed deletion mapping of 5p in 60 cases of invasive CC. We found that 60% of the tumors exhibit a 5p loss of heterozygosity (LOH). The patterns of LOH allowed us to identify two minimal regions of deletions, one at 5p15.3 spanning a 5.5 cM genetic distance and a second site of 7 cM at 5p15.2-15.3. In addition, we also identified 5p deletions in 16% lesions of high-grade cervical intraepithelial neoplasia (CIN). 5p LOH was found in 63% of HPV 16 positive tumors, while only 33% tumors with other HPV-types had 5p LOH. The differences in frequency of 5p LOH between tumors harboring HPV16 in combination with other HPV types and tumors harboring HPV16 DNA alone were significantly higher, suggesting a synergistic effect of high-risk types in causing genomic instability. Conclusion:These findings implicate the presence of tumor suppressor gene(s) on 5p relevant to CC tumorigenesis.

Background Converging points of evidence implicate infection by highrisk human papilloma virus (HPV) types as a critical etiologic factor in cervical tumorigenesis [1]. Epidemio

logical and experimental data, however, show that only a small fraction of HPVinfected cervical intraepithelial ne oplastic (CIN) lesions progress to invasive cervical carci noma (CC) [2]. These findings suggest somatic genetic

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