Deletion of Dinucleotide Repeat (Δ14 Allele) in the Methylthioadenosine Phosphorylase (MTAP) Promoter and the Allelotype of MTAP Promoter in the Japanese Population

5′‐Deoxy‐5′‐methylthioadenosine phosphorylase (MTAP) is an enzyme involved in purine and polyamine metabolism and is ubiquitously expressed in normal human tissues and cells. However, this enzyme has been found to be deficient in a variety of human cancers. Although the enzyme deficiency is known to be caused by MTAP gene deletion, human diffuse histiocytic lymphoma cell line DHL‐9 without any detectable MTAP activity has been found to possess the intact MTAP gene. These lines of evidence suggested that promoter abnormality might cause the MTAP deficiency in DHL‐9. Therefore, we analyzed the MTAP promoter region of DHL‐9 and found the deletion of 14 bases in its sequence. We designated the allele lacking (GT)(6)GC as dinucleotide repeat deletion (Δ14 allele) and determined the effect of the Δ14 allele on the MTAP promoter activity by a luciferase reporter assay. We have also analyzed the distribution of the Δ14 allele and wild‐type (WT) allele in the Japanese population by PCR assay. A reporter plasmid harboring the Δ14 allele exhibited luciferase activity comparable to that of a plasmid containing the WT allele. Forty‐six (22%) out of 210 people were homozygous for WT allele in the MTAP promoter, whereas 43 (20.5%) were homozygous for Δ14 allele. The remaining 121 people (57.5%) possessed Δ14/WT alleles in the MTAP promoter region. These results indicated that the Δ14 allele has nothing to do with MTAP deficiency in DHL‐9. The Δ14 allele is distributed among the general population irrespective of gender.