Loss of heterozygosity for loci on chromosome 6q in human malignant melanoma

Abstract

Restriction fragment length polymorphism (RFLP) analysis was used as a molecular genetic approach to examine loci on chromosome 6q for loss of constitutional heterozygosity (LOH). Five polymorphic DNA markers (that recognize RFLP's at specific chromosome 6q loci), and one polymorphic DNA marker for 6p were used to screen 20 autologous pairs of melanoma tumor DNA and normal blood DNA to determine the tumor and constitutional genotypes of each patient. LOH on chromosome 6q was identified at 21/53 informative loci (40%). Five patients had allele losses consistent with the loss of 6q (or of an entire copy of 6), and four other patients had terminal deletions of 6q. The chromosomal region bearing the highest frequency of 6q allele loss (60%) is defined by the marker loci c-MYB and ESR (q22-23 and q24-27). Comparison was then made with LOH observed at loci on four different chromosomes (1p, 11p, 16q and 17p) with results indicating a loss in 5% of cases. These results suggest that the loss of somatic sequences from chromosome 6q is a nonrandom and possibly biologically relevant event in human malignant melanoma.