A serine/threonine kinase gene defective in Peutz-Jeghers syndrome.
Studies of hereditary cancer syndromes have contributed greatly to our understanding of molecular events involved in tumorigenesis. Here we investigate the molecular background of the Peutz-Jeghers syndrome (PJS), a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems. A locus for this condition was recently assigned to chromosome 19p. We have identified truncating germline mutations in a gene residing on chromosome 19p in multiple individuals affected by PJS. This previously identified but unmapped gene, LKB1, has strong homology to a cytoplasmic Xenopus serine/threonine protein kinase XEEK1, and weaker similarity to many other protein kinases. Peutz-Jeghers syndrome is therefore the first cancer-susceptibility syndrome to be identified that is due to inactivating mutations in a protein kinase.
Hemminki
A
A
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
Markie
D
D
Tomlinson
I
I
Avizienyte
E
E
Roth
S
S
Loukola
A
A
Bignell
G
G
Warren
W
W
Aminoff
M
M
Höglund
P
P
Järvinen
H
H
Kristo
P
P
Pelin
K
K
Ridanpää
M
M
Salovaara
R
R
Toro
T
T
Bodmer
W
W
Olschwang
S
S
Olsen
A S
AS
Stratton
M R
MR
de la Chapelle
A
A
Aaltonen
L A
LA
D000091162:AMP-Activated Protein Kinase Kinases; D000595:Amino Acid Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010580:Peutz-Jeghers Syndrome / Q000201:enzymology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D029867:Xenopus Proteins
D029867:Xenopus Proteins; C100358:STK11 protein, Xenopus; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases