Unusually stable abnormal karyotype in a highly aggressive melanoma negative for telomerase activity

Abstract

ABSTRACT: Malignant melanomas are characterized by increased karyotypic complexity, extended aneuploidy and heteroploidy. We report a melanoma metastasis to the peritoneal cavity with an exceptionally stable, abnormal pseudodiploid karyotype as verified by G-Banding, subtelomeric, centromeric and quantitative Fluorescence in Situ Hybridization (FISH). Interestingly this tumor had no detectable telomerase activity as indicated by the Telomere Repeat Amplification Protocol. Telomeric Flow-FISH and quantitative telomeric FISH on mitotic preparations showed that malignant cells had relatively short telomeres. Microsatellite instability was ruled out by the allelic pattern of two major mononucleotide repeats. Our data suggest that a combination of melanoma specific genomic imbalances were sufficient and enough for this fatal tumor progression, that was not accompanied by genomic instability, telomerase activity, or the engagement of the alternative recombinatorial telomere lengthening pathway.