A serine/threonine kinase gene defective in Peutz-Jeghers syndrome

Nature. 1998 Jan 8;391(6663):184-7. doi: 10.1038/34432.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19
  • Female
  • Germ-Line Mutation
  • Humans
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Peutz-Jeghers Syndrome / enzymology
  • Peutz-Jeghers Syndrome / genetics*
  • Polymerase Chain Reaction
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Sequence Homology, Amino Acid
  • Xenopus Proteins*

Substances

  • Xenopus Proteins
  • STK11 protein, Xenopus
  • STK11 protein, human
  • Protein-Serine-Threonine Kinases