Deletion of chromosome 3p is an early event in malignant progression of cervical cancer

Background: Loss of chromosome 3p has been reported to be a common genetic alteration in certain types of armors as well as in cervical cancer. To understand its role in multistep cervical carcinogenesis, we analysed the allelic loss of this chromosome region in early pre-invasive cervical neoplastic lesions. Materials and Methods: 49 cases comprising two types of pre-invasive lesions (without and with coexisting invasive cancer) were selected. Chromosome 3p deletios in selected neoplastic lesions were detected by PCR-RFLP combined with morphologically guided microdissection technique for DNA preparation. Results: DNA samples from 40 cases out of 49 were successfully amplified and found to be heterozygotes at least in one chosen chromosome marker. Of 19 cases without coexisting cancer LOH was detected in 4 cases(21%) and 3/17(18%) precancerous lesions (1 moderate dysplasia, 2 severe dysplasias) and 1/5(20%) carcinomas-in-situ. A significantly higher rate of allelic loss was observed in pre-invasive lesions adjacent to invasive cancer, showing 29%(4/14) in precancerous lesion and 67%(2/3) in carcinoma-in-situ. Analysing the invasive cancel and synchronous pre-invasive neoplasia, LOH was found to occur at early precursor stage in the majority of cases(5/7). The most frequently lost locus in cervical cancer is the chromosome regions detected by marker D3S30(60%) and D3F15S2(47%), suggesting a candidate tumor supressor gene, which may play a role in cervical carcinogenesis is harboured on this chromosome region. Conclusions: Our results confirm the high frequency of chromosome 3p allelic loss in cervical cancer and suggest that this genetic alteration is an early event in the development of cervical cancer and may potentially serve as a marker of risk for progression of premalignant lesions to invasive cancer.