HIGH-RESOLUTION ANALYSIS OF CHROMOSOME 3P ALTERATIONS IN CERVICAL-CARCINOMA

Although loss of heterozygosity (LOH) for loci on chromosome 3p is a c ommon event in cervical carcinoma (CC), the frequency and affected reg ions of 3p are inconsistent among studies. Here we report a comprehens ive analysis of LOH on 3p in 66 primary tumors and 16 CC-derived cell lines using a high density of marker loci. Clonal LOH was found in ove r 70% of primary tumors, and the patterns of loss indicated four to fi ve target regions, with 3p14 being the most frequent. The majority of tumors had complex patterns of allelic imbalance, with regions of subc lonal and clonal losses often present in individual tumors. We exploit ed marker homozygosity in CC-derived cell lines as an indirect measure of LOH and identified four homozygous deletions (HDs) during this ana lysis at Loci located within the 3p14.2 region to which the FHIT gene has been mapped recently. This led to a careful reevaluation of the LO H patterns in primary CCs, which showed apparent retention of heterozy gosity for loci in this region indicative of the presence of several a dditional HDs. To our knowledge, this is the first report of HDs encom passing the FHIT gene region in primary tumor samples and underscores the usefulness of high resolution genetic analysis of tumor genomes in determining the chromosomal aberrations underlying the malignant prog ression of CC.