Extra copies of c-myc are more pronounced in nodular melanomas than in superficial spreading melanomas as revealed by fluorescence in situ hybridisation.

Abstract

Amplification of c-myc is a common genetic alteration and associated with a poor prognosis in a variety of cancers. Extra copies of the gene have been found in large numbers of melanoma metastases, but only few primary tumours have been studied. We investigated the c-myc copy number alterations in two different subtypes of primary melanomas with different biological behaviours. Fluorescence in situ hybridisation was performed using c-myc and centromeric 8 (C8) probes on 68 lesions (28 nodular melanomas [NMs], 26 superficial spreading melanomas [SSMs], and 14 metastases). To assess the ploidy pattern, copy number distribution of seven different chromosomes was also investigated. All tumours showed aneuploid populations for at least three chromosomes. Whereas 61% of the NMs exhibited extra c-myc copies, only 27% of SSMs showed increased gene dosage. The c-myc/C8 ratio exceeding 1.5 was significantly higher in NMs (P = 0.01). High level amplification was seen only in NMs. An elevated c-myc/C8 ratio was higher than 1.5 in only four metastases. Our data show that c-myc copy number alterations differ in the two melanoma subtypes and are associated with the advanced stage of the disease. The less frequent amplification of the c-myc gene in metastatic lesions indicates that it may play an important role in the development of an invasive potential rather than in the metastatic process.