CERVICAL INTRAEPITHELIAL NEOPLASIA-III SHOWS FREQUENT ALLELIC LOSS IN3P AND 6P

We have shown previously that a significant number of invasive cervica l cancers (ICC) have nonrandom chromosomal losses in 3p, 6p, 11q, 29, 6q, and 19q, thereby suggesting that genes involved in the suppression of tumor development or progression are located in these regions. Cer vical intraepithelial neoplasia (CIN) III is considered the precursor lesion for ICC of squamous type and occurs frequently with ICC of glan dular type. In an effort to define which chromosomal losses are presen t in the precursor lesions, we identified CIN III lesions from 24 ICC treated by radical hysterectomy. Thirty-three CIN III associated with 22 squamous carcinomas and 2 adenocarcinomas were carefully microdisse cted from the paraffin-embedded sections. The whole genomic DNA from C IN III was amplified with short random primers. DNA from ICC, CIN III, and normal tissue was analyzed at the six chromosomal regions with po lymorphic markers. Thirty-eight percent of hysterectomy specimens had loss of heterozygosity (LOH) in at least one of the CIN III lesions fr om each case. Loss occurred in 30% of cases in 3p14.1-12 (37% for asso ciated ICC), 21% in 6p23 (33%), 14% in 2q33-37 (27%), 0 in 11q23.3 (33 %), 4% in 19q13.4 (13%), and 0 in 6q21-23.3 (18%). These results sugge st that mutations in 3p and 6p are important early in tumorigenesis, w hereas 11q and 6q contain genes important later in tumor progression. Invasive and preinvasive cervical lesions appear to develop from multi focal genetic events since consistent losses do not occur within all p recursor lesions in the same patient. (C) 1998 Wiley-Liss, Inc.