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.

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

“…Loss of chromosome 19p13.3, which includes the GNG7 locus, has been observed frequently in several cancers (Ritland et al, 1995;Hoglund et al, 1998;Wang et al, 1999;Kato et al, 2004;Miyai et al, 2004;Yang et al, 2004). Furthermore, STK11, the Peutz -Jeghers gene, is also located on the telomeric region of chromosome 19p13.3 (Hemminki et al, 1998;Jenne et al, 1998). In our oesophageal cancer study, LOH in GNG7 region (19p13.3) was detected in 10 out of 40 patients (25%).…”

Missense Mutation of the MET Gene Detected in Human Glioma

“…The deletion of the MET locus on chromosome 7, as demonstrated by FISH data in the patient with a missense mutation (Case 3), may suggest the exclusive expression of the mutant allele by overrepresentation of the mutant allele (30) or loss of suppression effect of the wild-type allele, as shown in defective serine/threonine kinase gene (31).…”

Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

“…This phosphorylation is carried out by another serine/threonine kinase, LKB1 (Lizcano et al (2004); for review see Bardeesy et al, this issue). Germline loss-of-function mutations in the LKB1 gene are responsible for autosomal dominant Peutz-Jeghers syndrome, which is characterized by the development of benign hamartomatous polyps throughout the gastrointestinal tract (Hemminki et al, 1998). One of the most important features associated with Peutz-Jeghers syndrome is the increased risk of carcinomas from the stomach, colon, lung, uterus and breast.…”