MOLECULAR-GENETIC EVIDENCE FOR UNIFOCAL ORIGIN OF ADVANCED EPITHELIALOVARIAN-CANCER AND FOR MINOR CLONAL DIVERGENCE

Detection of loss of heterozygosity (LOH) and DNA Bow cytometry (FCM) were used to trace the origin of bilateral ovarian cancer from 16 pati ents. From each tumour the DNA index (DI) and LOH patterns for chromos omes 1, 3, 6, 11, 17, 18, 22 and X were determined with 36 microsatell ite markers. Formalin-fixed, paraffin-embedded as well as frozen speci mens were used. Flow cytometric cell sorting was used to enrich tumour cells for polymerase chain reaction (PCR)-driven LOH analysis. Analys is of the LOH data showed that in 12 of the 16 cases concordance was o bserved for all informative markers, namely retention of heterozygosit y (ROH) or loss of identical alleles in bath tumour samples. In four c ases discordant LOH patterns were observed. In two cases the discordan t LOH was found for one of the chromosomes tested while other LOH patt erns clearly indicated a unifocal origin. This suggests limited clonal divergence. In the other two cases all LOH patterns were discordant, most likely indicating an independent origin. The number of chromosome s showing LOH ranged from 0 to 6. Comparison of DNA FCM and the LOH da ta showed that the latter technique has a higher sensitivity for the d etection of a unifocal origin. In 14/16 cases evidence was found for a unifocal origin, while in two cases clonal divergence was found at LO H level and in two other cases clonal divergence at DNA ploidy level. In 12 cases the complete observed allelotype had developed before the formation of metastases, including the two cases showing a large DNA p loidy difference.