Frequent allelic imbalance of tumor suppressor gene loci in cervical dysplasia

In addition to human papillomavirus (HPV) infection, loss of heterozygosity (LOH) at tumor suppressor gene loci has been frequently observed in cervic al cancer. Thus, it may be assumed that detection and characterization of s pecific LOH profiles in preneoplastic lesions, in addition to HPV typing, m ight facilitate assessment of progression risk of cervical dysplasia. In th is study, the type and frequency of allelic imbalance (allelic loss or alle lic reduction) were analyzed in 24 unrelated cervical lesions using 14 poly morphic microsatellite markers at different tumor suppressor gene loci. No allelic loss was observed in four condylomatous lesions, whereas 2 of 13 (1 5%) CIN I lesions displayed allelic loss at 3p25 and 5q11-13. In high-grade lesions, however, allelic loss occurred in four of six (66%) cases at mult iple chromosomal regions (3p14-25, 5p15, 5q11, 5q21, 11p15, and 17q21). All elic 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 even t in cervical carcinogenesis. The detection of LOH on multiple chromosome 3 p loci in 50% of high-grade lesions suggests that a specific marker panel e ncompassing this region might enable better assessment of which lesions are likely to regress, persist, or progress.