INCREASED CHROMOSOME-20 COPY NUMBER DETECTED BY FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) IN MALIGNANT-MELANOMA

DNA amplification is an important mechanism of tumor progression that allows cancer cells to up-regulate the expression of critical genes su ch as oncogenes and genes conferring drug resistance. Recent studies u sing comparative genomic hybridization (CGH) revealed increased DNA co pies of 20q sequences in 7 melanoma cell lines and 8 archival metastat ic melanoma lesions. To evaluate chromosome 20 abnormalities in more d etail and to resolve discrepancies between karyotype and CGH findings, we performed FISH analysis of metaphase cells in 13 melanoma cell lin es (including the 7 lines used for CGH) and 9 primary melanoma specime ns by using a whole chromosome paint specific for chromosome 20. All 1 3 cell lines (100%) and 8/9 primary tumors (89%) showed extra copies o f chromosome 20 relative to tumor ploidy. Additionally, 6/14 cell line s (43%) and 2/8 primary tumors (25%) showed translocated chromosome 20 material previously undetected by standard cytogenetics. Cytologic ev idence for gene amplification was also found in one cell line, which c ontained an add(20)(p13), with additional DNA being derived from 20q s equences. These data suggest that overrepresentation of a gene or gene s important for melanoma pathogenesis resides on the long arm of chrom osome 20. (C) 1997 Wiley-Liss, Inc.