Malignant melanomas are divided into 2 major subtypes, depending on their locations: skin and eye melanomas, respectively. Skin melanomas are derived from epidermal melanocytes and reliant on genetic factors such as familial incidence, skin type, race and gender and environmental factors such as ultraviolet radiation. This tumor type is one of the most rapidly increasing malignancies among Caucasians and has a high mortality rate. In sporadic forms chromosomes 1, 6, 7, 9 and 10 are the chromosomes most commonly involved in somatic mutations.1 Structural rearrangements of chromosome 1 are especially frequent and include translocations, duplications and deletions, leading to loss of 1p. The most noted chromosome 6 changes have been nonreciprocal translocations leading to the loss of 6q, also frequently occurring as a consequence of isochromosome 6p formation. Although less frequent than 1p− and 6q−, loss of 9p is an important change in cutaneous melanomas as this loss involves the CDKN2A locus, known to predispose mutation carriers for melanocyte tumors.2 The frequent changes +7 and −10 have been associated with tumor progression.1 Uveal melanoma is the most common cancer of the eye and arises in the melanocytes of the uveal tract. Cytogenetic investigations have identified several recurrent clonal abnormalities such as loss of chromosome 3, gain of 8q and deletions of 6q. The gain of 8q may occur through several mechanisms such as isochromosome formation, unbalanced translocations and gain of a complete chromosome 8. An association between gain of chromosome 8 and loss of chromosome 3 may exist since these imbalances are frequently seen together.3, 4 Given the similar cellular origin of cutaneous and uveal melanomas, attention has been focused on defining tumor-specific karyotypic profiles. In this respect, −3, +8q and 1p− have been suggested to be specific for uveal melanomas and +6p and 6q− for cutaneous melanomas. However, these conclusions have been made from relatively small series of tumors and several investigators have reported frequent loss of 6q in uveal tumors5 as well as frequent loss of 3 and gain of 8q in cutaneous tumors.6
The high degree of karyotypic complexity in malignant melanomas makes it very difficult to discern possible cytogenetic subtypes. To overcome some of the difficulties caused by the composite nature of chromosomal changes in solid tumors, we have developed and adapted several statistical methods suitable for the analysis of complex karyotypes.7, 8 In the present investigation, we applied these methods to the 307 malignant melanomas reported in the Mitelman Database of Chromosome Aberrations in Cancer9 and to 55 previously unpublished cases of uveal melanomas. We constructed a genomic imbalance map and used this map to identify the most frequent imbalances. Tumors were then classified with respect to the presence or absence of these imbalances and statistically analyzed, in order to identify and assess karyotypic profiles, the chronological order of the imbalances as well as to identify possible karyotypic pathways.