Title :

AXIN2 germline testing in a French cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer

Author(s) :

Leclerc, Julie [Auteur]
Beaumont, Marie [Auteur]
Vibert, Roseline [Auteur]
Pinson, Stéphane [Auteur]
Vermaut, Catherine [Auteur]
Flament, Cathy [Auteur]
Lovecchio, Tonio [Auteur]
Delattre, Lucie [Auteur]
Demay, Christophe [Auteur]
Coulet, Florence [Auteur]
Guillerm, Erell [Auteur]
Hamzaoui, Nadim [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Benusiglio, Patrick [Auteur]
Brahimi, Afane [Auteur]
Cornelis, François [Auteur]
Delhomelle, Hélène [Auteur]
Fert-Ferrer, Sandra [Auteur]
Fournier, Benjamin [Auteur]
Physiopathologie orale moléculaire = Molecular Oral Pathophysiology [CRC]
Hovnanian, Alain [Auteur]
Genetic skin diseases : from disease mechanism to therapies [Equipe Inserm U1163]
Legrand, Clémentine [Auteur]
Lortholary, Alain [Auteur]
Malka, David [Auteur]
Petit, Florence [Auteur]
Saurin, Jean‐christophe [Auteur]
Lejeune, Sophie [Auteur]
Colas, Chrystelle [Auteur]
Buisine, Marie‐pierre [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]

Journal title :

Genes, Chromosomes & Cancer

Pages :

210-222

Publisher :

Wiley

Publication date :

2023-04

ISSN :

1045-2257

English keyword(s) :

adenomatous polyposis
colorectal cancer susceptibility
oligodontia
Wnt signaling pathway

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. ...
Show more >Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. To assess the clinical relevance for AXIN2 testing in patients suspected of genetic predisposition to CRC, we collected clinical and molecular data from the French Oncogenetics laboratories analyzing AXIN2 in this context. Between 2004 and June 2020, 10 different pathogenic/likely pathogenic AXIN2 variants were identified in 11 unrelated individuals. Eight variants were from a consecutive series of 3322 patients, which represents a frequency of 0.24%. However, loss‐of‐function AXIN2 variants were strongly associated with genetic predisposition to CRC as compared with controls (odds ratio: 11.89, 95% confidence interval: 5.103–28.93). Most of the variants were predicted to produce an AXIN2 protein devoid of the SMAD3‐binding and DIX domains, but preserving the β‐catenin‐binding domain. Ninety‐one percent of the AXIN2 variant carriers who underwent colonoscopy had adenomatous polyposis. Forty percent of the variant carriers developed colorectal or/and other digestive cancer. Multiple tooth agenesis was present in at least 60% of them. Our report provides further evidence for a role of AXIN2 in CRC susceptibility, arguing for AXIN2 testing in patients with colorectal adenomatous polyposis or cancer.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Submission date :

2024-02-17T03:32:25Z