ANALYSIS OF THE RETINOBLASTOMA TUMOR-SUPPRESSOR GENE IN PANCREATIC ENDOCRINE TUMORS

OBJECTIVES The molecular pathogenesis of human pancreatic endocrine tu mours (PETs) is largely unknown. One attractive candidate gene for inv olvement in pancreatic endocrine neoplasia is the retinoblastoma (Rb) tumour suppressor gene, A deletion of the Rb gene was recently describ ed in a human insulinoma, In addition, mice harbouring a null mutation in the Rb gene bred with p53 mutant mice develop pancreatic endocrine tumours, Therefore, we sought to determine the role that allelic loss of Rb may play in a large series of human pancreatic endocrine tumour s. PATIENTS AND MEASUREMENTS 46 pancreatic endocrine tumours were obta ined from 41 patients, Utilizing genomic DNA isolated from the tumour samples and control normal cells, 2 highly polymorphic microsatellite loci (D13S153 and Rb 1.20) located within the Rb gene were PCR amplifi ed and examined for loss of heterozygosity, RESULTS 2 patients were ho mozygous at both loci and thus uninformative, The remaining 39 had inf ormative markers at one or both of these loci, and none of the tumours from these patients demonstrated allelic loss of Rb. CONCLUSIONS In t umours in which Rb inactivation is pathogenetically important, somatic loss of one Rb allele commonly accompanies a point mutation or microd eletion within the other allele, Thus, the absence of demonstrable all elic loss in this large series strongly suggests that Rb gene inactiva tion is not frequently involved in the pathogenesis of human pancreati c endocrine tumours.