THE HUMAN-LEUKOCYTE ANTIGEN TAP2 GENE DEFINES THE CENTROMERIC LIMIT OF MELANOMA SUSCEPTIBILITY ON CHROMOSOME 6P

A single human leukocyte antigen (HLA) class II allele, DQB10301, is strongly associated with melanoma, and the HLA-DR locus provides the t elomeric boundary for melanoma susceptibility in the HLA class II regi on of chromosome 6. However, the centromeric boundary is unknown. This study was designed to determine whether the adjacent upstream transpo rter associated with antigen processing (TAP) locus, TAP2, constitutes the centromeric boundary of disease susceptibility in melanoma. Molec ular oligotyping of TAP2 genes was performed for 36 Caucasian patients with melanoma and for 32 Caucasian control individuals by both amplif ication refractory mutation system (ARMS) polymerase chain reaction (P CR) and PCR-sequence-specific oligonucleotide (SSO) typing. TAP2 allel e frequencies in the melanoma patients were compared to those in non-m elanoma Caucasian control populations, and to HLA-DQ allele frequencie s determined by molecular oligotyping. While HLA-DQB10301 was more co mmon in this group of 36 melanoma patients compared to a group of 200 controls (56 percent vs. 27 percent, Bonferoni-corrected chi-square p< =0.01), no significant differences were observed in TAP2 allele freque ncies between melanoma patients and controls. The TAP2 locus represent s the centromeric boundary of disease susceptibility for melanoma in t he class II region of chromosome 6p. These results support an etiologi c role for HLA-DQB10301 in melanoma susceptibility.