Publication

Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder

Gómez García, E. B. & Knoers, N. V. A. M., Jul-2009, In : Lancet Oncology. 10, 7, p. 727-735 9 p.

Research output: Contribution to journalReview articleAcademicpeer-review

APA

Gómez García, E. B., & Knoers, N. V. A. M. (2009). Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder. Lancet Oncology, 10(7), 727-735. https://doi.org/10.1016/S1470-2045(09)70167-6

Author

Gómez García, Encarna B ; Knoers, Nine V A M. / Gardner's syndrome (familial adenomatous polyposis) : a cilia-related disorder. In: Lancet Oncology. 2009 ; Vol. 10, No. 7. pp. 727-735.

Harvard

Gómez García, EB & Knoers, NVAM 2009, 'Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder', Lancet Oncology, vol. 10, no. 7, pp. 727-735. https://doi.org/10.1016/S1470-2045(09)70167-6

Standard

Gardner's syndrome (familial adenomatous polyposis) : a cilia-related disorder. / Gómez García, Encarna B; Knoers, Nine V A M.

In: Lancet Oncology, Vol. 10, No. 7, 07.2009, p. 727-735.

Research output: Contribution to journalReview articleAcademicpeer-review

Vancouver

Gómez García EB, Knoers NVAM. Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder. Lancet Oncology. 2009 Jul;10(7):727-735. https://doi.org/10.1016/S1470-2045(09)70167-6


BibTeX

@article{c875fec35b104263985f66c3fcbb1090,
title = "Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder",
abstract = "Familial adenomatous polyposis (FAP) is an autosomal dominant form of intestinal polyposis and colorectal cancer caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. The term Gardner's syndrome is used to describe extracolonic manifestations, such as osteomas, skin cysts, congenital hypertrophy of the retinal pigmented epithelium (CHRPE), and desmoid tumours (aggressive fibromatosis), that are especially prominent in families with FAP. We postulate that a ciliary dysfunction is the underlying pathogenetic mechanism of extraintestinal manifestations in patients with FAP. This postulation is based on the presence of common clinical manifestations (ie, cysts, retinal abnormalities, and fibrosis) in Gardner's syndrome and cilia-related disorders. Additionally, both APC and the cilia have degradation of beta-catenin as the common downstream target in the Wnt-signalling pathway. Mutations in APC causing Gardner's syndrome are clustered in a region encoding a series of amino-acid repeats responsible for the binding to beta-catenin. Proofs of principle that beta-catenin could be the key mediator of the ciliary disorder also rely in the findings that overexpression of beta-catenin induces polycystic kidney disease, and CHRPE phenotypes in animal models. Other candidates for the common link between Gardner's syndrome and cilia-related disorders are the APC-binding proteins: end-binding protein 1 (EB1) and kinesin-family-member 3a (KIF3a), both of which are ciliary proteins involved in intraflagellar transport. Finally, pathogenetic similarities between some ciliopathies and extraintestinal tumours in FAP suggest a cilia defect. Understanding extracolonic manifestations in the context of FAP as a ciliary disorder might add new therapeutic options for patients with Gardner's syndrome.",
keywords = "Ciliary Motility Disorders/genetics, Gardner Syndrome/genetics, Genes, APC, Genotype, Humans, Microtubule-Associated Proteins/genetics, Mutation/genetics, Phenotype, Signal Transduction/genetics, beta Catenin/genetics",
author = "{G{\'o}mez Garc{\'i}a}, {Encarna B} and Knoers, {Nine V A M}",
year = "2009",
month = "7",
doi = "10.1016/S1470-2045(09)70167-6",
language = "English",
volume = "10",
pages = "727--735",
journal = "Lancet Oncology",
issn = "1470-2045",
publisher = "ELSEVIER SCIENCE INC",
number = "7",

}

RIS

TY - JOUR

T1 - Gardner's syndrome (familial adenomatous polyposis)

T2 - a cilia-related disorder

AU - Gómez García, Encarna B

AU - Knoers, Nine V A M

PY - 2009/7

Y1 - 2009/7

N2 - Familial adenomatous polyposis (FAP) is an autosomal dominant form of intestinal polyposis and colorectal cancer caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. The term Gardner's syndrome is used to describe extracolonic manifestations, such as osteomas, skin cysts, congenital hypertrophy of the retinal pigmented epithelium (CHRPE), and desmoid tumours (aggressive fibromatosis), that are especially prominent in families with FAP. We postulate that a ciliary dysfunction is the underlying pathogenetic mechanism of extraintestinal manifestations in patients with FAP. This postulation is based on the presence of common clinical manifestations (ie, cysts, retinal abnormalities, and fibrosis) in Gardner's syndrome and cilia-related disorders. Additionally, both APC and the cilia have degradation of beta-catenin as the common downstream target in the Wnt-signalling pathway. Mutations in APC causing Gardner's syndrome are clustered in a region encoding a series of amino-acid repeats responsible for the binding to beta-catenin. Proofs of principle that beta-catenin could be the key mediator of the ciliary disorder also rely in the findings that overexpression of beta-catenin induces polycystic kidney disease, and CHRPE phenotypes in animal models. Other candidates for the common link between Gardner's syndrome and cilia-related disorders are the APC-binding proteins: end-binding protein 1 (EB1) and kinesin-family-member 3a (KIF3a), both of which are ciliary proteins involved in intraflagellar transport. Finally, pathogenetic similarities between some ciliopathies and extraintestinal tumours in FAP suggest a cilia defect. Understanding extracolonic manifestations in the context of FAP as a ciliary disorder might add new therapeutic options for patients with Gardner's syndrome.

AB - Familial adenomatous polyposis (FAP) is an autosomal dominant form of intestinal polyposis and colorectal cancer caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. The term Gardner's syndrome is used to describe extracolonic manifestations, such as osteomas, skin cysts, congenital hypertrophy of the retinal pigmented epithelium (CHRPE), and desmoid tumours (aggressive fibromatosis), that are especially prominent in families with FAP. We postulate that a ciliary dysfunction is the underlying pathogenetic mechanism of extraintestinal manifestations in patients with FAP. This postulation is based on the presence of common clinical manifestations (ie, cysts, retinal abnormalities, and fibrosis) in Gardner's syndrome and cilia-related disorders. Additionally, both APC and the cilia have degradation of beta-catenin as the common downstream target in the Wnt-signalling pathway. Mutations in APC causing Gardner's syndrome are clustered in a region encoding a series of amino-acid repeats responsible for the binding to beta-catenin. Proofs of principle that beta-catenin could be the key mediator of the ciliary disorder also rely in the findings that overexpression of beta-catenin induces polycystic kidney disease, and CHRPE phenotypes in animal models. Other candidates for the common link between Gardner's syndrome and cilia-related disorders are the APC-binding proteins: end-binding protein 1 (EB1) and kinesin-family-member 3a (KIF3a), both of which are ciliary proteins involved in intraflagellar transport. Finally, pathogenetic similarities between some ciliopathies and extraintestinal tumours in FAP suggest a cilia defect. Understanding extracolonic manifestations in the context of FAP as a ciliary disorder might add new therapeutic options for patients with Gardner's syndrome.

KW - Ciliary Motility Disorders/genetics

KW - Gardner Syndrome/genetics

KW - Genes, APC

KW - Genotype

KW - Humans

KW - Microtubule-Associated Proteins/genetics

KW - Mutation/genetics

KW - Phenotype

KW - Signal Transduction/genetics

KW - beta Catenin/genetics

U2 - 10.1016/S1470-2045(09)70167-6

DO - 10.1016/S1470-2045(09)70167-6

M3 - Review article

VL - 10

SP - 727

EP - 735

JO - Lancet Oncology

JF - Lancet Oncology

SN - 1470-2045

IS - 7

ER -

ID: 92703453