IDENTIFICATION OF THE MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 (MEN1) GENE

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant di sorder characterised by tumours of the parathyroids, pancreas and ante rior pituitary that represents one of the familial cancer syndromes. T he MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centromerically by PYGM and telomeri cally by D11S1783 defined by combined meiotic and tumour deletion mapp ing studies. Two candidate genes, ZFM1 and PPP2R5B, from this region h ave been previously excluded, and in order to identify additional cand idate genes we used a BAC to isolate cDNAs from a bovine parathyroid c DNA library by direct selection. One of the novel genes that we identi fied, SCG2, proved to be identical to the recently published MEN1 gene , which is likely to be a tumour suppressor gene. The SCG2 transcript was 2.9 kb in all tissues with an additional 4.2 kb transcript also be ing present in the pancreas and thymus. Mutational analysis of SCG2 in 10 unrelated MEN1 families identified one polymorphism and nine diffe rent heterozygous mutations (one missense, four non-sense, one inserti onal and three deletional frameshifts) that segregated with the diseas e, hence providing an independent confirmation for the identification of the MEN1 gene.