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

@article{Hemminki1998ASK,
  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},
  journal={Nature},
  year={1998},
  volume={391},
  pages={184-187}
}
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

A novel germline frameshift mutation (757-758insT) in the LKB1 gene is found and a marked reduction in L KB1 protein expression in the carcinoma cells, suggesting that the loss of LKB 1 function may have led to the carcinogenesis of the gastric cancer.

A role for LKB1 gene in human cancer beyond the Peutz–Jeghers syndrome

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.

The mouse Peutz-Jeghers syndrome gene Lkb1 encodes a nuclear protein kinase.

It is shown that Lkb1 is most likely a nuclear protein and a nuclear localization signal within the protein sequence is defined, indicating that the defect in Peutz-Jeghers syndrome may directly result in changes in gene expression in the nucleus of target cells.

Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma

The data suggest that LKB1/STK11 may contribute to tumorigenesis in a small fraction of malignant melanomas.

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

Direct evidence is provided that the elimination of the kinase activity of LKB1 is probably responsible for the development of the PJS phenotypes and the elucidation of the molecular etiology of PJS and the positional cloning of the second potential PJS gene will further elucidate the involvement of kinases/phosphatases in theDevelopment of cancer-predisposing syndromes.

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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