RELATIONSHIPS BETWEEN UMPK AND PGD ACTIVITIES AND DELETIONS OF CHROMOSOME 1P IN COLORECTAL CANCERS

A deletion involving a large segment of the short arm of chromosome 1(1p-) occurs in about 50% of colorectal cancers. It was previously noticed that, in these tumors, many deletions affect genes encoding for enzymes of the de novo pathway of nucleotide synthesis. The gene for uridine monophosphate kinase (UMPK), mapped on 1p32, is generally involved in del(1p). The activity of the corresponding enzyme was measured and compared to that of 6-phosphogluconate dehydrogenase (PGD), encoded by a gene also mapped on chromosome 1p and frequently deleted, but involved in another metabolism. It was found that a clear relationship exists between activity and the number of chromosome 1p for PGD but not for UMPK, both on primary tumors (PTs) and on tumors grafted into nude mice (GTs). By comparison to corresponding normal mucosae, the activity of PGD was high in PTs and GTs, but this increase was reduced in case of del(1p). The activity of UMPK being increased in PTs but not in GTs, it is assumed that the increase in PTs is due to non-cancerous cells, which are missing in GTs. The fact that no gene dosage effect exists, although the tendency for del(1p) coexists with the relative decrease of UMPK activity in cancerous by comparison to non-cancerous cells, suggests that either mutation or disregulation of UMPK gene occurred early.