English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/240516
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Germline variation in O6-methylguanine-DNA methyltransferase (MGMT) as cause of hereditary colorectal cancer

AuthorsBelhadj, Sami; Moutinho, Cátia; Mur, Pilar; Setien, Fernando; Llinàs-Arias, Pere; Pérez-Salvia, Montserrat; Pons, Tirso CSIC ORCID ; Pineda, Marta; Brunet, Joan; Navarro, Matilde; Capellá, Gabriel; Esteller, Manel; Valle, Laura
KeywordsMGMT
Hereditary cancer
Cancer genetics
Epimutation
Promoter hypermethylation
Issue Date10-Apr-2019
PublisherElsevier
CitationCancer Letters 447: 86-92 (2019)
AbstractSomatic epigenetic inactivation of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) is frequent in colorectal cancer (CRC); however, its involvement in CRC predisposition remains unexplored. We assessed the role and relevance of MGMT germline mutations and epimutations in familial and early-onset CRC. Mutation and promoter methylation screenings were performed in 473 familial and/or early-onset mismatch repair-proficient nonpolyposis CRC cases. No constitutional MGMT inactivation by promoter methylation was observed. Of six rare heterozygous germline variants identified, c.346C > T (p.H116Y) and c.476G > A (p.R159Q), detected in three and one families respectively, affected highly conserved residues and showed segregation with cancer in available family members. In vitro, neither p.H116Y nor p.R159Q caused statistically significant reduction of MGMT repair activity. No evidence of somatic second hits was found in the studied tumors. Case-control data showed over-representation of c.346C > T (p.H116Y) in familial CRC compared to controls, but no overall association of MGMT mutations with CRC predisposition. In conclusion, germline mutations and constitutional epimutations in MGMT are not major players in hereditary CRC. Nevertheless, the over-representation of c.346C > T (p.H116Y) in our familial CRC cohort warrants further research.
Description© 2019 The Authors.
Publisher version (URL)http://dx.doi.org/10.1016/j.canlet.2019.01.019
URIhttp://hdl.handle.net/10261/240516
Identifiersdoi: 10.1016/j.canlet.2019.01.019
issn: 0304-3835
Appears in Collections:(CNB) Artículos
Files in This Item:
File Description SizeFormat 
Germline_Belhadj_PV_Art2019.pdf603,12 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.