title: Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases.
abstract: Amplification and overexpression of the c-myc gene have been associated with neoplastic transformation in a plethora of malignant tumours. We applied interphase fluorescence in situ hybridization (FISH) with a locus-specific probe for the c-myc gene (8q24) in combination with a corresponding chromosome 8 alpha-satellite probe to evaluate genetic alterations in 8 primary melanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spreads of 7 melanoma cell lines a whole chromosome 8 paint probe was used. We investigated the functionality of the c-myc gene by detecting c-myc RNA expression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals relative to the centromere of chromosome 8 copy number. None of the nevi, safety margins or normal skin samples demonstrated this gain. In 2/7 melanoma cell lines (C32 and WM 266-4) isochromosome 8q formation with a relative gain of c-myc copies and a loss of 8p was observed. The highest c-myc gene expression compared to GAPDH was found in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%) expressed the c-myc gene on a lower level. 72.7% of the patients with c-myc extra copies had visceral melanoma metastases (UICC IV), patients without c-myc gain in 35.0% only. The collective with additional c-myc copies also expressed the gene on a significantly higher level. These results indicate that a c-myc gain in relation to the centromere 8 copy number might be associated with advanced cutaneous melanoma.
authors.affiliation: Department of Dermatology, University of Ulm, Ulm, Germany.
authors.forename: G M
authors.initials: GM
authors.lastname: Kraehn
authors.forename: J
authors.initials: J
authors.lastname: Utikal
authors.forename: M
authors.initials: M
authors.lastname: Udart
authors.forename: K M
authors.initials: KM
authors.lastname: Greulich
authors.forename: G
authors.initials: G
authors.lastname: Bezold
authors.forename: P
authors.initials: P
authors.lastname: Kaskel
authors.forename: U
authors.initials: U
authors.lastname: Leiter
authors.forename: R U
authors.initials: RU
authors.lastname: Peter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured
chemical_list: D005987:Glyceraldehyde-3-Phosphate Dehydrogenases