MECHANISMS OF HUMAN-MELANOMA CELL-GROWTH AND TUMOR SUPPRESSION BY CHROMOSOME-6

Breaks and deletions of chromosome 6 are among the most frequent karyo typic abnormalities that appear in human malignant melanoma cells, and chromosome transfer experiments have provided functional evidence for the presence of a melanoma tumor suppressor locus on chromosome 6 [J. M. Trent et al., Science (Washington DC), 247: 568-571, 1990], We hav e investigated the genetic mechanism of this suppression, We have foun d that the suppression of tumorigenicity that follows the introduction of a normal copy of chromosome 6 into the UACC 903 human melanoma cel l line is correlated with increased chromosome 6 dosage, rather than w ith the presence of the transferred normal copy of the chromosome, Tra nsfer of chromosome 6 into another human melanoma cell line, MelJuSo, does not result in suppression of primary tumor formation, although th e additional copy of chromosome 6 does reduce the cell growth rate in vitro. Finally, we have identified a substantial portion of the chromo some that is evidently not involved in tumor suppression, We have obse rved that a copy of chromosome 6 derived from a normal cell but with a deletion involving chromosome bands 6q22-6q24 suppresses primary tumo r formation in UACC 903 cells as effectively as the intact chromosome, We have thus provided additional information about the chromosomal lo cation of this tumor suppressor and about its mode of action.