Hamartomatous Polyposis Syndromes: Peutz–Jeghers Syndrome and Familial Juvenile Polyposis

Abstract

The hamartomatous polyposes are rare syndromes but provide fascinating insights into both the different mechanisms by which cancer can develop and the precursor lesions involved.

Keywords: colon; rectum; cancer; hamartoma; polyposis; PJS; JPS

References

Boardman LA, Couch FJ, Burgart LJ, et al. (2000) Genetic heterogeneity in Peutz–Jeghers syndrome. Human Mutation 16(1): 23–30.

Hemminki A (1999) The molecular basis and clinical aspects of Peutz–Jeghers syndrome. Cellular and Molecular Life Sciences 55(5): 735–750 (review).

Hemminki A, Markie D, Tomlinson I, et al. (1998) A serine/threonine kinase gene defective in Peutz–Jeghers syndrome. Nature 391(6663): 184–187.

Hemminki A, Tomlinson I, Markie D, et al. (1997) Localization of a susceptibility locus for Peutz–Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nature Genetics 15(1): 87–90.

Howe JR, Bair JL, Sayed MG, et al. (2001) Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nature Genetics 28(2): 184–187.

Howe JR, Roth S, Ringold JC, et al. (1998) Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280(5366): 1086–1088.

McGarrity TJ, Kulin HE and Zaino RJ (2000) Peutz–Jeghers syndrome. American Journal of Gastroenterology 95(3): 596–604 (review).

Miyaki M, Iijima T, Hosono K, et al. (2000) Somatic mutations of LKB1 and beta‐catenin genes in gastrointestinal polyps from patients with Peutz–Jeghers syndrome. Cancer Research 60(22): 6311–6313.

Olschwang S, Markie D, Seal S, et al. (1998) Peutz–Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3. Journal of Medical Genetics 35(1): 42–44.

Westerman AM, Entius MM, de Baar E, et al. (1999) Peutz–Jeghers syndrome: 78‐year follow‐up of the original family. Lancet 353(9160): 1211–1215.

Further Reading

Houlston R, Bevan S, Williams A, et al. (1998) Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. Human Molecular Genetics 7(12): 1907–1912.

Sapkota GP, Kieloch A, Lizcano JM, et al. (2001) Phosphorylation of the protein kinase mutated in Peutz–Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP‐dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell growth. Journal of Biological Chemistry 276(22): 19469–19482.

Wang ZJ, Churchman M, Avizienyte E, et al. (1999) Germline mutations of the LKB1 (STK11) gene in Peutz–Jeghers patients. Journal of Medical Genetics 36(5): 365–368.

Wang ZJ, Taylor F, Churchman M, Norbury G and Tomlinson I (1998) Genetic pathways of colorectal carcinogenesis rarely involve the PTEN and LKB1 genes outside the inherited hamartoma syndromes. American Journal of Pathology 153(2): 363–366.

Woodford‐Richens K, Bevan S, Churchman M, et al. (2000) Analysis of genetic and phenotypic heterogeneity in juvenile polyposis. Gut 46(5): 656–660.

Woodford‐Richens KL, Rowan AJ, Poulsom R, et al. (2001) Comprehensive analysis of SMAD4 mutations and protein expression in juvenile polyposis: evidence for a distinct genetic pathway and polyp morphology in SMAD4 mutation carriers. American Journal of Pathology 159(4): 1293–1300.

Woodford‐Richens K, Williamson J, Bevan S, et al. (2000) Allelic loss at SMAD4 in polyps from juvenile polyposis patients and use of fluorescence in situ hybridization to demonstrate clonal origin of the epithelium. Cancer Research 60(9): 2477–2482.

Zhou XP, Woodford‐Richens K, Lehtonen R, et al. (2001) Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan–Riley–Ruvalcaba syndromes. American Journal of Human Genetics 69(4): 704–711.

Web Links

Bone morphogenetic protein receptor, type IA (BMPR1A); Locus ID: 657. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=657

MAD, mothers against decapentaplegic homolog 4 (Drosophila) (MADH4); Locus ID: 4089. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4089

Serine/threonine kinase 11 (Peutz–Jeghers syndrome) (STK11); Locus ID: 6794. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6794

Bone morphogenetic protein receptor, type IA (BMPR1A); MIM number: 601299. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?601299

MAD, mothers against decapentaplegic homolog 4 (Drosophila) (MADH4); MIM number: 600993. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?600993

Serine/threonine kinase 11 (Peutz–Jeghers syndrome) (STK11); MIM number: 602216. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?602216

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Tomlinson, Ian PM(Jan 2006) Hamartomatous Polyposis Syndromes: Peutz–Jeghers Syndrome and Familial Juvenile Polyposis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005997]