A serine/threonine kinase gene defective in Peutz-Jeghers syndrome.
Hemminki A,
Markie D,
Tomlinson I,
Avizienyte E,
Roth S,
Loukola A,
Bignell G,
Warren W,
Aminoff M,
Höglund P,
Järvinen H,
Kristo P,
Pelin K,
Ridanpää M,
Salovaara R,
Toro T,
Bodmer W,
Olschwang S,
Olsen AS,
Stratton MR,
de la Chapelle A,
Aaltonen LA.
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
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.
PMID: 9428765 [PubMed - indexed for MEDLINE]