Intragenic homozygous deletions of MTS1 gene in gastric cancer in Taiwan.

The multiple tumor suppressor 1 (MTS1) and 2 (MTS2) genes, located on chromosome 9p21, have been reported to be deleted or mutated in many malignant cell lines and in a high percentage of some primary carcinomas. To determine whether these genes are altered, and if so, what is the nature of the alterations, in human gastric adenocarcinoma, we investigated their frequency of mutation by Southern blotting, polymerase chain reaction (PCR) and direct sequencing in 55 patients. Furthermore, loss of heterozygosity (LOH) of chromosome 9p21 at the IFNA locus and D9S171 was assessed. Homozygous deletions of exon 1 of the MTS1 gene were identified in 5 of 55 (9.1%) primary tumors. No deletion of MTS2 gene was noted. LOH was observed in 7 (14.3%) of 49 informative cases (5 cases at IFNA locus, 2 cases at D9S171 and one case with combined LOH at D9S171 and homozygous deletion at exon 1 of MTS1). Direct sequencing of PCR products of the MTS1 and MTS2 gene did not reveal any point mutation in these 55 patients. These data indicate that alterations of the MTS1 and MTS2 genes are infrequently encountered. Additional studies of LOH with more microsatellite markers near 9p21 are mandatory to elucidate whether another tumor suppressor gene exists in the vicinity of MTS1 in primary gastric adenocarcinoma.