A malignant melanoma tumor suppressor on human chromosome 11

Abstract

Considerable molecular genetic and cytogenetic evidence indicates that chromosome 11 is a target for chromosome breakage, rearrangement, and loss during the development of human malignant melanomas. Abnormalities of the long arm of chromosome 11 are also evident in a wide variety of other human solid tumors, including carcinomas of the breast, ovary, cervix, and lung. In melanomas, these abnormalities tend to cluster in the lower half of the long arm of chromosome 11, indicating the possible presence of a melanoma tumor suppressor gene in this region. We tested this possibility by using microcell-mediated chromosome transfer to introduce normal copies of human chromosome 11 into two human malignant melanoma cell lines. In one cell line, MelJuSo, the presence of an additional copy of chromosome 11 severely reduced the ability of the cells to grow in culture. In a second cell line, UACC 903, there was a moderate reduction in cell growth in vitro, and the ability of the hybrid cells to form tumors in animals was suppressed. Suppression of tumorigenicity was even more strongly pronounced in a microcell hybrid that received an isochromosome 11q derived from the donor copy of chromosome 11. The formation of tumors was accompanied by a reduction in the copy number of chromosome 11. This provides functional evidence that a melanoma tumor suppressor resides on the long arm of chromosome 11. Thus, a third distinct locus, in addition to those previously defined on chromosomes 6 and 9, appears to play a role in the development of human malignant melanoma.