title: A serine/threonine kinase gene defective in Peutz-Jeghers syndrome.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Hemminki
authors.forename: D
authors.initials: D
authors.lastname: Markie
authors.forename: I
authors.initials: I
authors.lastname: Tomlinson
authors.forename: E
authors.initials: E
authors.lastname: Avizienyte
authors.forename: S
authors.initials: S
authors.lastname: Roth
authors.forename: A
authors.initials: A
authors.lastname: Loukola
authors.forename: G
authors.initials: G
authors.lastname: Bignell
authors.forename: W
authors.initials: W
authors.lastname: Warren
authors.forename: M
authors.initials: M
authors.lastname: Aminoff
authors.forename: P
authors.initials: P
authors.lastname: Höglund
authors.forename: H
authors.initials: H
authors.lastname: Järvinen
authors.forename: P
authors.initials: P
authors.lastname: Kristo
authors.forename: K
authors.initials: K
authors.lastname: Pelin
authors.forename: M
authors.initials: M
authors.lastname: Ridanpää
authors.forename: R
authors.initials: R
authors.lastname: Salovaara
authors.forename: T
authors.initials: T
authors.lastname: Toro
authors.forename: W
authors.initials: W
authors.lastname: Bodmer
authors.forename: S
authors.initials: S
authors.lastname: Olschwang
authors.forename: A S
authors.initials: AS
authors.lastname: Olsen
authors.forename: M R
authors.initials: MR
authors.lastname: Stratton
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: 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
chemical_list: D029867:Xenopus Proteins; C100358:STK11 protein, Xenopus; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases