Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases

Amplification and overexpression of the c-myc gene have been associated wit h 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 chromos ome 8 alpha -satellite probe to evaluate genetic alterations in 8 primary m elanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spr eads 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 ex pression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals re lative to the centromere of chromosome 8 copy number. None of the nevi, saf ety 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 ga in of c-myc copies and a loss of 8p was observed. The highest c-myc gene ex pression 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 leve l. 72.7% of the patients with c-myc extra copies had visceral melanoma meta stases (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 hi gher level. These results indicate that a c-myc gain in relation to the cen tromere 8 copy number might be associated with advanced cutaneous melanoma. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.