Confirmation of the Germ Cell Origin of Ovarian Tumours Using a Standard Panel of Microsatellite Markers
A Adamiak, I Schrader, J Senz, CB Gilks, DG Huntsman. University of British Columbia, Vancouver, BC, Canada; BC Cancer Agency, Vancouver, BC, Canada
Background: Ovarian germ cell tumours are believed to arise from post meiotic germ cells and global lack of heterozygosity has been previously reported in 7/8 mature ovarian teratomas. Ovarian mucinous tumours are currently classified as surface-epithelial tumours, but have been suggested by some as arising out of a monodermal teratoma. The purpose of the study was to determine if any mucinous tumors could be proven to be of germ cell origin.
Design: Frozen tissue from 6 ovarian germ cell tumours (2 teratomas, 2 yolk sac tumours, 1 immature teratoma and 1 dysgerminoma), and 6 mucinous tumours (mucinous intraepithelial carcinomas and carcinomas) were included in the study. DNA was extracted, and genotyping performed using AmpFLSTR (Applied Biosystems), a standard PCR based forensic assay. The assay used includes 14 highly polymorphic short tandem repeats. FISH was performed on one case using a multiplexed 4 probe assay designed to detect aneusomy in breast cancer (Abbot Molecular).
Results: The dysgerminoma, 2/2 yolk sac tumours, 1/2 teratomas, and 2/2 mucinous tumours showed a heterozygous genetic profile (ie. diploid). One out of the two teratomas, and the immature teratoma were found to be monoalleic at all loci tested. FISH performed on these two cases demonstrated at least two copies of each of the four chromosomes assessed, suggesting these tumors arose from non-segregation during meiosis II or through a post-meitotic duplication of chromosomes. As occasional heterozygosity due to meiotic recombination at meiosis I would be expected in meiosis II errors the latter is more likely. Analysis of the other tumors is ongoing.
Conclusions: DNA genotyping using a standard microsatellite panel can elucidate the histogenesis of ovarian carcinomas. These results demonstrate that the majority of germ cell tumors are not of post-meiotic origin. One of the mature teratomas and an immature teratoma showed global lack of heterozygosity, suggesting at least some of these tumors arise from meiosis II or post meiotic errors. We were not able to prove germ cell origin for 2/2 mucinous tumors.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 165, Wednesday Morning