THE PHOSPHOLIPASE-C BETA-3 GENE LOCATED IN THE MEN1 REGION SHOWS LOSSOF EXPRESSION IN ENDOCRINE TUMORS

Oncogenesis of tumours related to multiple endocrine neoplasia type 1 (MEN1) is associated with somatic deletions involving the MEN1 locus, suggesting inactivation of a tumour suppressor gene in this region. Id entification of meiotic cross-overs in MEN1 families has placed the ME N1 locus centromeric of D11S807. An extended deletion mapping was perf ormed in 27 primary parathyroid tumours, and identified D11S427 as the closest centromeric flanking marker. Through physical mapping using n ewly isolated cDNA clones, we estimated the distance between the flank ing markers D11S807 and D11S427 to be less than 900 kb. One of these c DNA clones showed expression of a 4.4 kb message in multiple tissues, including those affected in MEN1, while in five endocrine tumours no t ranscript was detected. Sequence characterization showed that this gen e encodes for the phospholipase C beta 3, a key enzyme in signal trans duction.