Mapping the sites of putative tumor suppressor genes at 6p25 and 6p21.3 incervical carcinoma: Occurrence of allelic deletions in precancerous lesions

Allelic deletions on the short arm of chromosome 6 (6p) are one of the comm on, possibly early, genetic changes that occur in the pathogenesis of cervi cal carcinoma (CC), Previous loss of heterozygosity (LOH) studies in CC ide ntified a number of critical regions of deletions on 6p, However, the preci se location of minimally deleted regions and their role in precancerous les ions have not been well characterized. To address these questions, we first performed a detailed LOH analysis on 6p in 59 cases of invasive CC. The pa ttern of LOH identified two minimal regions of deletions, one spanning a 5 cM genetic distance at 6p25 and a second site of 10.3 cM deletion mapping t o 6p21.3. The 6p21.3 minimal deletion spans HLA class I genes. To understan d the role of 6p genetic alterations in the development of CC, we also inve stigated 12 high-grade and 4 low-grade cases of cervical intraepithelial ne oplasia (CIN) for LOH after laser microdissection, The high-grade CINs exhi bited 91.7% LOH, and low-grade CINs had 50% LOH, These Findings implicate t he presence of at least two tumor suppressor genes on 6p relevant to CC and suggest that these genetic alterations occur very early in CC development. This study should therefore facilitate the identification of tumor suppres sor genes on 6p and may identify which CINs are at high risk of progressing to invasive CC.