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Frequent allelic imbalance of tumor suppressor gene loci in cervical dysplasia

Item Type:Article
Title:Frequent allelic imbalance of tumor suppressor gene loci in cervical dysplasia
Creators Name:Luft, F.C. and Gebert, J. and Schneider, A. and Melsheimer, P. and von Knebel-Doeberitz, M.
Abstract:In addition to human papillomavirus (HPV) infection, loss of heterozygosity (LOH) at tumor suppressor gene loci has been frequently observed in cervical cancer. Thus, it may be assumed that detection and characterization of specific LOH profiles in preneoplastic lesions, in addition to HPV typing, might facilitate assessment of progression risk of cervical dysplasia. In this study, the type and frequency of allelic imbalance (allelic loss or allelic reduction) were analyzed in 24 unrelated cervical lesions using 14 polymorphic microsatellite markers at different tumor suppressr gene loci. No allelic loss was observed in four condylomatous lesions, whereas 2 of 13 (15%) CIN I lesions displayed allelic loss at 3p25 and 5q11-13. In high-grade lesions, however, allelic loss occured in four of six (66%) cases at multiple chromosomal regions (3p14-25, 5p15, 5q11, 5q21, 11p15 and 17q21). Allelic reduction was observed in 4 of 13 (30%) low-grade lesions and 3 of 6 (50%) high-grade lesions. LOH was confined to lesions infected by high-risk HPV types. These data suggest that chromosomal instability is an early event in cervical carcinogenesis. The detection of LOH on multiple chromosome 3p loci in 50% of high-grade lesions suggest that a specific marker panel encompassing this region might enable better assessment of which lesions are likely to regress, persist, or progress.
Keywords:Loss Of Heterozygosity (LOH), Cervical Intraepithelial Neoplasia (CIN), Human Papillomavirus (HPV) Infection
Source:International Journal of Gynecological Pathology
Publisher:Lippincott Williams & Wilkins
Page Range:374-380
Date:October 1999
PubMed:View item in PubMed

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