Comparative genomic hybridization detects genetic alterations during earlystages of cervical cancer progression

Invasive cervical carcinoma is thought to arise from cervical intraepitheli al neoplasm (CIN). Genetic changes that occur during progression of CIN to cervical carcinoma are poorly understood, although they appear to be direct ly involved in this process. We used comparative genomic hybridization (CGH ) with precise microdissection and degenerate oligonucleotide primed-polyme rase chain reaction (DOP-PCR) to detect genetic alterations in normal epith elial, CIN, and invasive carcinoma tissues colocalized in tumors from 18 pa tients with squamous cell carcinoma of the uterine cervix. Gains on chromos ome I and on 3q and losses on 2q, 3p, 4, 6p, 11q, and 17p were frequent alt erations found in CIN and invasive carcinoma lesions. Interestingly, severa l of these genetic changes were observed in preinvasive carcinoma lesions. The frequency and average number of genetic alterations corresponded direct ly to the extent to which the cervical carcinoma had progressed. Frequent a lterations were found in more than 90% of CIN III lesions. Gains on 3q and losses on 11q were the most prevalent genetic alterations found in associat ion with uterine cervix carcinogenesis. The common regions of alteration we re 3q26.1-q28 and 11q23-qter. The majority of tumor samples showed variabil ity in genetic alterations across lesion types within a single specimen. (C ) 2002 Wiley-Liss, Inc.