Iournal zyxwvutsrqponm of Internal Medicine zyxwvutsrqpo 1995; 238: 245-248 zyxwvutsrqp Candidate genes for multiple endocrine neoplasia type 1 J. LAGERCRANTZ,' C. LARSSON,' S. GRIMMOND,' B. SKOGSEID,3 A. GOBL,3 E. FRIEDMAN,' E. CARSON,' C. PHELAN,'.' K. OBERG,3 M. NORDENSKJOLD,' N. K. HAYWARD' zyx & G. WEBER' From the ' kpartment 01 Molecular Medicine. Cliniral Genetics Unit. Karolinska Hospital. Stockholm, Sweden, ' Qeensland ZnstitutP zyx o/ Medical Researrh. Human Genetics Laboratory. Herston. Qeensland, Australia, ' Department of Internal Medicine, University Hospital. Uppsala. Sweden, M.D. Anderson Cuncer Center. Department o/ Endocrinologu. Houston. Texas, USA. and ' Department of Medicine. Division of Medical Genetics. Montreal General Hospital. Montreal, Quebec, Cunada Abstract. Lagercrantz J, Larsson C. Grimmond S, Skogseid B. Gob1 A. Friedman E. Carson E, Phelan C. Oberg K. Nordenskjold M. Hayward NK, Weber G (Department of Molecular Medicine, Clinical Genetics Unit. Karolinska Hospital, Stockholm, Sweden, Queensland Institute of Medical Research, Human Genetics Laboratory, Herston, Queensland, Australia, Department of Internal Medicine, University Hospital, Uppsala. Sweden, M. D. Anderson Cancer Center, Department of Endocrinology, Houston, Texas, USA, Department of Medicine, Division of Medical Genetics, Montreal General Hospital, Montreal, Quebec, Canada). Candidate genes for multiple endocrine neoplasia type 1 (Minisymposium : Multiple Endocrine Neoplasia 1). I Intern Med 1995; 238: 245-8. The aim of this study was to isolate and characterize candidates for the multiple endocrine neoplasia type 1 (MEN1)gene. The development of tumours related to MENl is associated with somatic deletions in- volving the MENl locus, suggesting inactivation of a tumour-suppressor gene in this region. We have isolated five cDNA candidates located within the 900 kb remaining for the MENl gene, determined their sequence, and characterized their expression in normal tissues and several endocrine tumours. One of the candidates, encoding for phospholipase C-83, showed properties consistent with the idea of a tumour-suppressor gene. Keywords: candidate genes, chromosome 1 1, MEN 1, PLCB3. Introduction The predisposing genetic defect in multiple endocrine neoplasia type 1 (MENl) has been assigned to chromosomal region 1 l q l 3 based on allelotyping of pancreatic tumours and subsequent linkage analysis [ 11. Combined tumour and pedigree genotype analy- zyxwv sis showed that allele losses in MEN1-associated tumours eliminated the allele at 1 lq13 derived from the unaffected parent. The MENl gene thereby matched the criteria for being a tumour-suppressor gene, according to Knudson's model first applied on retinoblastoma [2]. Somatic deletions that encompass the MENl locus have also been found in sporadic counterparts to the MEN 1-associated tumours. i.e. primary hyperparathyroidism, pancreatic islet cell tumours and a few anterior pituitary adenomas, in varying frequencies depending on the tumour type. As described in detail in another paper in this issue (Teh et d.), the polymorphic markers DllS807 and DllS427 were shown to flank the MENl locus. Through physical mapping, we estimated the dis- Q 1995 Blackwell Science Ltd 24 5