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

  title={A serine/threonine kinase gene defective in Peutz–Jeghers syndrome},
  author={Akseli Hemminki and David M. Markie and Ian P. M. Tomlinson and Egle Avizienyte and Stina Roth and Anu Loukola and Graham Bignell and William Warren and Maria Aminoff and Pia H{\"o}glund and Heikki J{\"a}rvinen and Paula Kristo and Katarina Pelin and Maaret Ridanpää and Reijo Salovaara and Tumi T. Toro and Walter F. Bodmer and Sylviane Olschwang and Anne S. Olsen and Michael R. Stratton and Albert de la Chapelle and Lauri A. Aaltonen},
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 (ref. 3). We have identified truncating germline mutations in a gene residing on chromosome 19p in… 

A novel germline mutation of the LKB1 gene in a patient with Peutz-Jeghers syndrome with early-onset gastric cancer

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The present review considers the frequency and pattern of LKB1 gene mutations in sporadic cancers of various origins, and the role of the encoded protein in cancer development.

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Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity.

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De novo germline mutation in the serine–threonine kinase STK11/LKB1 gene associated with Peutz–Jeghers syndrome

DNA from microdissected gastrointestinal hamartomatous polyps in the PJS patient was isolated and the loss of heterozygosity (LOH) at the LKB1 locus was investigated by real‐time fluorescence polymerase chain reaction genotyping using a fluorescent resonance energy transfer technique, suggesting a different mechanism from LOH in the formation of hamarto- polyps.

Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients

P predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial contexts, despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features.

Mutations in the human LKB1/STK11 gene

A review of the literature provides a total of 40 different somatic LKB1 mutations in 41 sporadic tumors and seven cancer cell lines, which are concordant with the germline mutation spectrum.

Somatic mutations in LKB1 are rare in sporadic colorectal and testicular tumors.

Somatic mutations of LKB1 are not frequent in colorectal and testicular cancer, suggesting that the gene may function as a tumor suppressor.

Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer.

The results indicate that STK 11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.



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Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis

A search for a putative tumour suppressor locus was made using comparative genomic hybridization of Peutz-Jeghers polyps, combined with loss of heterozygosity (LOH), and molecular evidence of malignant potential in hamartomas is provided.

Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma

An Arg24Cys mutation in CDK4 is described, which generates a dominant oncogene that is resistant to normal physiological inhibition by p16INK4a in two unrelated melanoma families which do not carry germline p16inks4a mutations.

Increased risk of cancer in the Peutz-Jeghers syndrome.

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The widespread expression of MOX1 in non-embryonal tissues suggests a role in normal cell biology which warrants further study and represents an attractive candidate for the BRCA1 gene.

Cloning and Characterization of a Novel Serine/Threonine Protein Kinase Expressed in Early Xenopus Embryos*

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A metric physical map of human chromosome 19 has been generated and currently, the map consists of 51 ‘islands’ containing multiple clone types, whose size, order and relative distance are known.

Lessons from Hereditary Colorectal Cancer

Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance.

Discussion Table 2 and 3 summarize data concerning our 10 proved cases of intestinal polyposis that manifested a distinctive variety of melanin spots of the oral mucosa, lips and digits. The ages of