The +24 base pair mutation cosegregates with melanoma and myeloma in family A, and the wild type allele is deleted in the malignant plasma cells of patient No. II:1.

Shaded members denote cancer development with the cancer type given below. The arrow indicates the proband with multiple myeloma. Four individuals in family A have developed melanoma (patients No. I:1, II:2, II:5, and II:7). The positions of the wild type, mutant, and heteroduplex bands are indicated on the right-hand side of the figure. Note that all 5 individuals harboring the +24 mutation have developed cancer, while patients No. I:2, II:4, and II:6 are wild type for both alleles and have not developed any malignancy. (DNA was not available for patient No. II:3.) On the left side of the figure, the PCR reactions from germline, unsorted BM, and sorted BM cells are shown under patient No. II:1. Note that the LOH of the wild typeCDKN2A allele is seen only in the sorted (greater than 90% malignant plasma cells) obtained from this individual. Importantly, there is a large decrease in the amount of heteroduplex DNA present in the sorted BM sample, which was again due to lack of the wild type PCR product.