Mutational analysis ofPPARGas a candidate tumour suppressor gene in enteropancreatic endocrine tumours.

Loss of heterozygosity (LOH) or deletion of chromosome 3p is a frequent finding in enteropancreatic endocrine tumours (EPETs), suggesting the pathogenetic involvement of one or more tumour suppressor genes on 3p.PPARG, the gene encoding the gamma isoform of the peroxisome proliferator-activated receptor (PPARγ), is highly expressed in normal human pancreatic islet cells, is located at 3p25, and has been reported to sustain loss-of-function mutations in human colorectal carcinomas. Additionally, the development of islet cell hyperplasia in an islet cell-specificppargknockout mouse has further emphasized the attractiveness ofPPARGas a candidate gene important in the pathogenesis of EPETs. Therefore, we sought to examinePPARGfor intragenic inactivating mutations, the evidence needed to rigorously establish it as a tumour suppressor in EPETs.Twenty-three EPETs from 20 patients were examined for coding region mutations inPPARGand for LOH on 3p at microsatellite markers flankingPPARG.LOH on 3p was detected in tumours from six patients (30%), but no intragenic mutations were detected inPPARG, whether or not LOH was present.These findings strongly suggest thatPPARGdoes not commonly function as a classical tumour suppressor gene in the pathogenesis of EPETs. [ABSTRACT FROM AUTHOR]