Deletion of dinucleotide repeat (Delta 14 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 (Delta 14 allele) and determined the effect of the Delta 14 allele on the MTAP promoter activity by a luciferase reporter assay. We have also analyzed the distribution of the Delta 14 allele and wild-type (WT) allele in the Japanese population by PCR assay. A reporter plasmid harboring the Delta 14 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 Delta 14 allele. The remaining 121 people (57.5%) possessed Delta 14/WT alleles in the MTAP promoter region. These results indicated that the Delta 14 allele has nothing to do with MTAP deficiency in DHL-9. The Delta 14 allele is distributed among the general population irrespective of gender.

5′‐deoxy‐5′‐methylthioadenosine phosphorylase

diffuse histiocytic lymphoma‐9

5′‐deoxy‐5′‐methylthioadenosine

reverse transcriptase‐polymerase chain reaction

phosphate‐buffered saline

slipped strand mispairing