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

@article{Hemminki1997LocalizationOA,
  title={Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis},
  author={Akseli Hemminki and Ian P. M. Tomlinson and David M. Markie and Heikki J{\"a}rvinen and Pertti Sistonen and A M Bj{\"o}rkqvist and Sakari Knuutila and Reijo Salovaara and Walter F. Bodmer and Darryl Shibata and Albert de la Chapelle and Lauri A. Aaltonen},
  journal={Nature Genetics},
  year={1997},
  volume={15},
  pages={87-90}
}
Many human cancer susceptibility genes have been successfully mapped by genetic linkage studies1. One that has so far eluded researchers is that for Peutz-Jeghers (P-J) syndrome, a condition characterized by intestinal hamartomatous polyposis and melanin spots of the lips, buccal mucosa and digits2,3. A dramatically elevated risk of malignancy has also been documented4. Gastrointestinal tumours as well as cancers of the breast, ovary, testis and uterine cervix appear to be overrepresented in… 

Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4.

Results confirm the mapping of a common P JS locus on 19p13.3 but also suggest the existence, in a minority of families, of a potential second PJS locus, on 19q13.4.

Pathogenesis of Adenocarcinoma in Peutz-Jeghers Syndrome1

Evidence is provided that STK1ÃŒis a tumor suppressor gene that acts as an early gatekeeper regulating the development of hamartomas in PJS and suggest that Hamartomas may be pathogenetic precursors of adenocarcinoma.

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.

Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome.

Analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families with JPS and 11 sporadic cases, suggesting at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24.

Complete germline deletion of the STK11 gene in a family with Peutz–Jeghers syndrome

This report, which constitutes the first description of a complete germline deletion of STK11, shows that the presence of such large genomic deletions should be considered in PJS families without detectable point mutations ofSTK11.

Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome

Evidence is provided that STK11/LKB1 acts as a tumour suppressor gene, and may be involved in the early stages of PJS tumorigenesis, which suggests the presence of a distinct pathway of carcinogenesis.

Advances in Brief Pathogenesis of Adenocarcinoma in Peutz-Jeghers Syndrome 1

Evidence is provided that STK1 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.

Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz‐Jeghers' syndrome provides evidence for a hamartoma–(adenoma)–carcinoma sequence

Molecular evidence that Peutz‐Jeghers' syndrome patients are predisposed to cancers at several sites is provided, as a direct result of selection for loss of the ‘wild‐type’ LKB1 allele in tumours.

Allele loss and mutation screen at the Peutz-Jeghers (LKB1) locus (19p13.3) in sporadic ovarian tumours

It appears that LKB1 mutations can cause ovarian tumours when present in the germline, but occur rarely in the soma, similar to BRCA1 and BRC a2.
...

References

SHOWING 1-10 OF 12 REFERENCES

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.

Neoplastic transformation arising in Peutz-Jeghers polyposis

Neoplastic transformation is not a rare event, and the results may indicate evidence of a hamartoma-adenoma-carcinoma sequence in Peutz-Jeghers polyposis.

Somatic microsatellite mutations as molecular tumor clocks

The genetic legacy inherent to multistep tumorigenesis provides direct estimates of tumor ages, with up to thousands of cell divisions and high death rates necessary to yield the observed diversities.

Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors.

Comparative genomic hybridization produces a map of DNA sequence copy number as a function of chromosomal location throughout the entire genome, which identified 16 different regions of amplification, many in loci not previously known to be amplified.

Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors

Recent optimized procedures for CGH are described, including DNA labeling, hybridization, fluorescence microscopy, digital image analysis, data interpretation, and quality control, emphasizing those steps that are most critical.

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

Familial adenomatous polyposis and other polyposis syndromes

History and registries pathology genetics congenital hypertrophy of the retinal pigment epithelium imaging, endoscopy, radiology, computerized tomography of desmoid tumours surgery-colectomy and

The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set–recoding and fuzzy inheritance

A novel set–recoding scheme is used to recode each person's genotype and ‘fuzzy inheritance’ to infer transmission probabilities and VITESSE enables fast and precise multipoint mappin of disease loci with highly polymorphic markers.

Specific genetic analysis of microscopic tissue after selective ultraviolet radiation fractionation and the polymerase chain reaction.

A method using selective ultraviolet radiation fractionation followed by polymerase chain reaction (PCR) can analyze specific cell subsets present on a microscope section to allow the specific and sensitive molecular genetic analysis of small numbers of cells histologically identified and selected under the microscope.

Faster sequential genetic linkage computations.

A variety of algorithmic improvements are described, which synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.