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© 1994 Oxford University Press

OTHER

The phospholipase C ß3 gene located in the MEN1 region shows loss of expression in endocrine tumours

Günther Weber1,*, Eitan Friedman1, Sean Grimmond2, Nicholas K. Hayward2, Catherine Phelan1, Britt Skogseid3, Anders Gobl3, Jan Zedenius1,4, Kerstin Sandelin4, Bin Tean Teh1,2, Emma Carson1, Irene White1, Kjell Öberg3, Joseph Shepherd5, Magnus Nordenskjöld1 and Catharina Larsson1

1Department of Clinical Genetics, Karolinska Hospital S-171 76 Stockholm, Sweden 2Queensland Cancer Fund Research Unit, Joint Experimental Oncology Program, Queensland, Institute for Medical Research, Herston Queensland 4029, Australia 3Department of Internal Medicine, University Hospital S-751 85 Uppsala 4Department of Surgery, Karolinska Hospital S-104 01 Stockholm, Sweden 5Department of Surgery, University of Tasmania, Royal Hobart Hospital Hobart, Tasmania 700, Australia

*To whom correspondence should be addressed

Received May 16, 1994; Revised August 4, 1994; Accepted August 4, 1994

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. Identification of meiotic cross-overs in MEN1 families has placed the MEN1 locus centromeric of D11S807. An extended deletion mapping was performed in 27 primary parathyroid tumours, and identified D11S427 as the closest centromeric flanking marker. Through physical mapping using newly isolated cDNA clones, we estimated the distance between the flanking markers D11S807 and D11S427 to be less than 900 kb. One of these cDNA clones showed expression of a 4.4 kb message in multiple tissues, including those affected in MEN1, while in five endocrine tumours no transcript was detected. Sequence characterization showed that this gene encodes for the phospholipase C ß3, a key enzyme in signal transduction.


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