Peutz-Jeghers syndrome is caused by mutations in a novel serine threoninekinase

  title={Peutz-Jeghers syndrome is caused by mutations in a novel serine threoninekinase},
  author={Dieter E. Jenne and Heike Reomann and Junichi Nezu and W Friedel and Steffan Loff and Reinhard Jeschke and Oliver M{\"u}ller and Walter Back and Michael Zimmer},
  journal={Nature Genetics},
Peutz-Jeghers (PJ) syndrome is an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. The PJ gene was recently mapped to chromosome 19p13.3 by linkage analysis, with the highest lod score at marker D195886. In a distance of 190 kb proximal to D195886, we identified and characterized a novel human gene encoding the serine threonine kinase STK11… 

Mutations analysis ofSTK11 gene in Chinese families with Peutz-Jeghers syndrome

Mutation frequency is higher in the families suffering PJS in three or more generations than that of the sporadic cases, indicating that the point mutation inSTK11 might be involved in PJS patho-genesis.

Genetic heterogeneity in Peutz‐Jeghers syndrome

Mutation analysis revealed genetic alterations in LKB1 in two probands who had a family history of PJS, suggesting the presence of significant genetic heterogeneity for PJS and the involvement of other loci in this syndrome.

Three novel mutations of STK11 gene in Chinese patients with Peutz–Jeghers syndrome

These findings broaden the mutation spectrum of the STK11 gene and would help clinicians and genetic counselors provide better clinical surveillance for PJS patients, especially for ones carrying truncating mutation.

Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome.

Evidence is provided that STK11 is a tumor suppressor gene that acts as an early gatekeeper regulating the development of hamartomas in PJS and suggest that hamartoma may be pathogenetic precursors of adenocarcinoma.

Novel mutations in the LKB1/STK11 gene in Dutch Peutz‐Jeghers families

The diverse array of mutations found, the apparent high mutation rate, as well as the existence of a possible second PJS locus, renders diagnostic or predictive genetic testing in individual patients difficult, although future identification of additional mutations or even gene(s) will help in increasing the yield of direct mutation analysis.

One novel deletion and one splicing mutation of the LKB1 gene in two Chinese patients with Peutz-Jeghers syndrome.

Support is provided that mutation of the L KB1 gene is a cause of Peutz-Jeghers syndrome, and the spectrum of LKB1 gene mutations is expanded.

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 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.

Must Peutz-Jeghers syndrome patients have the LKB1/STK11 gene mutation? A case report and review of the literature

This study suggests that some other genetic disorders may cause PJS besides LKB1/STK11 gene mutation, and suggests that missense mutations in APC and MSH6 gene may lead to abnormalities in structure and function of their expression products, and may result in the occurrence of PJS.

Lack of STK11 gene expression in homozygous twins with Peutz-Jeghers syndrome.

Investigating abnormal expression of the STK11 gene may serve as a molecular approach to the diagnosis of PJS and may facilitate genotype-phenotype correlations in PJS patients.



Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome

Mutational analysis of PTEN in CD kindreds has identified germline mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene, and implies that PTEN may play a role in organizing the relationship of different cell types within an organ during development.

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.

Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p.

It is found that all carriers expressed the PJS phenotype and no noncarriers displayed PJS sequellae, indicating complete penetrance with no sporadic cases, and no evidence for genetic heterogeneity is found.

Increased risk of cancer in the Peutz-Jeghers syndrome.

It is suggested that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.

Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.

The data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS.

Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers

The results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.

Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers.

A gene, MCC, which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor is identified and is a candidate for the putative colorectal tumor suppressor gene located at chromosome region 5q21.

Cancer and the Peutz-Jeghers syndrome.

There is evidence for a hamartoma/carcinoma sequence in the Peutz-Jeghers syndrome, suggesting that the gene locus involved is relevant to the development of malignancy in general.

PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer

Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation of a candidate tumor suppressor gene, PTEN, that appears to be mutated at considerable frequency in human cancers.