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Loss of Heterozygosity for Loci on the Long Arm of Chromosome 6 in Human Malignant Melanoma¹

Arizona Cancer Center [D. M.] and Committee on Genetics [C. W.], University of Arizona, Tucson, Arizona 85724; Department of Radiation Oncology [E. M., J. T.] and Human Genetics [J. T.], The University of Michigan, Ann Arbor, MI 48109-0668; and The Oncology Center [B. V.], Johns Hopkins University, Baltimore, MD 21205

Malignant melanoma has been documented to display recurring abnormalities of chromosome 6, particularly the long arm (6q). Restriction fragment length polymorphism analysis was used as a molecular genetic approach to examine loci on chromosome 6q for loss of constitutional heterozygosity (LOH). Five DNA markers that recognize restriction fragment length polymorphisms along 6q and one polymorphic DNA marker for 6p were used to screen 20 autologous pairs of tumor DNA and normal DNA to determine the tumor and constitutional genotypes of each patient. LOH on chromosome 6q was identified at 21 of 53 informative loci (40%). Five patients with more than one informative locus had allele losses consistent with the loss of the entire long arm (or of an entire copy) of chromosome 6, while four other patients demonstrated terminal deletions of 6q. The chromosomal region bearing the highest frequency of 6q allelic loss (60%) is defined by the marker loci c-MYB and ESR (6q22–23 and 6q24–27). In contrast to the frequency of 6q loss, LOH was observed at loci on four other chromosomes (1, 11, 16, 17) in only 5% of cases. These results have led us to conclude that the loss of sequences from the long arm of chromosome 6 is a nonrandom and possibly biologically relevant event in human malignant melanoma.

¹ Supported in part by PHHS Grants CA-29476 and CA-41183 awarded by the National Cancer Institute, Bethesda, MD.

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, MSRBII C560B, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0668.

Received 5/14/91. Accepted 8/ 1/91.

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