Loss of Heterozygosity on the Short Arm of Chromosome 3 in Cervical Intra-Epithelial Neoplasia without Concomitant Cervical Carcinoma

Abstract

Losses of heterozygosity on the short arm of chromosome 3p are common in cervical carcinomas in the 3p13-3p21 region, and can be observed in intra-epipthelial lesions accompanying cervical cancers. As a preliminary attempt to determine whether these losses can be observed in intra-epithelial cervical lesions without concomitant invasive carcinoma, we have used two microsatellite markers located at the two most frequently deleted segments of the 3p13-3p21 region. We have studied 36 cases of grade II and grade III cervical intra-epithelial neoplasias obtained by conisation biopsies and 30 cases of cervical carcinoma including 3 micro-invasive squamous cell carcinomas. We found loss of heterozygosity or microsatellite instability in 6 of 16 (38%) and 9 of 23 (39%) informative cases of cervical carcinoma at 3p13 and 3p21, respectively. Four of 27 (15%) cases of cervical intra-epithelial neoplasia showed loss of heterozygosity at 3p13, whereas loss of heterozygosity or microsatellite instability at 3p21 was found in 5 of 19 cases (26%). No relationship was found between 3p loss of heterozygosity and human papillomavirus infection. In conclusion, losses of heterozygosity at 3p13 and 3p21 occur in premalignant lesions without concomitant invasive lesions. The prevalence and precise extent of these losses should be established by a more extensive analysis.

Genetic deletion and human papillomavirus infection in cervical cancer: Loss of heterozygosity sites at 3p and 5p are important genetic events

“…In a cervical-cancer cell line, integrated HPV DNA has been identified at a fragile site FRA3B within the FHIT locus (Greenspan et al, 1997). Our data indicate the important role of 3p deletion, a ''high-risk''-HPV-typeassociated genetic event, in the development of cervical cancer, as supported by the observation of 3p deletion in pre-cancerous lesions of cervical cancer (Wistuba et al, 1997;Fouret et al, 1998).…”

“…This present analysis of LOH at 3p and 5p in relation to ''high-risk'' HPV types 16/18 is of special interest. We have reported a common region of deletion at 5p both in pre-cancerous and in cancerous lesions (Mitra et al, 1995), and deletions have also been reported at 3p in pre-cancerous lesions of cervical carcinoma (Wistuba et al, 1997;Fouret et al, 1998). In view of the present data and other reported observations, it seems likely that multiple genetic events, such as deletion/mutation at 3p and 5p in association with HPV infection, are relevant in the development of cervical cancer.…”

Microsatellite Instability, Expression of hMSH2 and hMLH1 and HPV Infection in Cervical Cancer and Their Clinico-Pathological Association

“…Fouret et al [11] found loss of heterozygosity or MSI in 6 of 16 (38%) and 9 of 23 (39%) informative cases of cervical carcinoma at 3p13 and 3p21, respective-ly. Mitra et al [12] observed MSI in 6 (13%) of 46 cases of cervical carcinoma using 5 microsatellite loci (D5S392, D5S406, D5S208, D5S117 and D5S432) mapped to 5p.…”

Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas

“…Moreover, 3p and 6p were also involved at the early precancer stages and during progression of cervical intraepithelial neoplasia to invasive cervical cancer (Larson et al, 1997b;Wistuba et al, 1997;Fouret et al, 1998;Guo et al, 1998Guo et al, , 2000Guo et al, , 2001Umayahara et al, 2002). Different studies reported various 3p LOH rates in the range 50-76% (Wistuba et al, 1997;Braga et al, 1999;Guo et al, 2000;Helland et al, 2000;Herzog et al, 2001;Acevedo et al, 2002).…”