The phospholipase C beta 3 gene located in the MEN1 region shows loss of expression in endocrine tumours.
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 beta 3, a key enzyme in signal transduction.
Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden.
G
G
Weber
E
E
Friedman
S
S
Grimmond
N K
NK
Hayward
C
C
Phelan
B
B
Skogseid
A
A
Gobl
J
J
Zedenius
K
K
Sandelin
B T
BT
Teh
D015152:Blotting, Northern; D002503:Centromere; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000201:enzymology / Q000235:genetics*; D009928:Organ Specificity; D010179:Pancreas / Q000201:enzymology; D010282:Parathyroid Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D015398:Signal Transduction; D014158:Transcription, Genetic; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; D005819:Genetic Markers; D007527:Isoenzymes; D015347:RNA Probes; D010738:Type C Phospholipases