Nonrandom chromosomal aberrations and associated oncogene alterations in human malignant melanoma
Cytogenetic analysis of seventeen tumors derived from eight patients revealed the nonrandom association of aberrations of chromosomes 1, 2, 3, 6, 7, and 9 with malignant melanoma. Aberrations of chromosomes 1 and 9 were identified in all seventeen tumors, including eight tumors derived from one patient. Aberrations of chromosome 2 were identified in fifteen of seventeen tumors. Similarly, aberrations of chromosomes 3 and 7 were identified in thirteen and sixteen tumors, respectively. Marker chromosomes involving chromosome 6 were observed in eight tumors. These results indicate that aberrations of chromosomes 1 and 9 are associated with the development of human malignant melanoma, and that aberrations of chromosome 9 are specific for malignant melanoma. The results further suggest that aberrations of chromosomes 2, 3, 6, and 7 may play a role in the progression and metastasis of the neoplasia, but not in the process of transformation Tumor heterogeneity was demonstrated by the identification of lesion specific markers in each tumor. In addition, in eight lesions derived from one patient and in two lesions derived from each of two different patients, common markers were identified. The presence of common markers in multiple lesions from the same patient indicate the clonal origin of the tumors Known oncogene loci were consistently and nonrandomly involved in the breakpoints identified on chromosomes 1, 2, 3, 7, and 9. Molecular analysis of four oncogenes, N-ras, N-myc, c-raf-1, and c-abl, located on chromosomes 1, 2, 3, and 9, respectively, showed that multiple oncogenes are altered at very high frequencies in human malignant melanoma. Correlative analysis of aberrations detected at the cytogenetic level and oncogene alterations detected at the molecular level indicated that genomic genomic disturbance of these oncogenes is correlated with the involvement of the oncogene-bearing chromosomes in marker chromosome formation. These results suggest that involvement of multiple oncogene-bearing chromosomes in marker formation is characteristic of malignant neoplasia