The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer

Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 protein...

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Main Authors:	Esteban-Jurado, Clara, Franch-Expósito, Sebastià, Muñoz, Jenifer, Ocaña, Teresa, Carballal, Sabela, López-Cerón, Maria, Cuatrecasas, Miriam, Vila-Casadesús, Maria, Lozano, Juan José, Serra, Enric, Beltran, Sergi, Brea-Fernández, Alejandro, Ruiz-Ponte, Clara, Castells, Antoni, Bujanda, Luis, Garre, Pilar, Caldés, Trinidad, Cubiella, Joaquín, Balaguer, Francesc, Castellví-Bel, Sergi
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027689/

id	pubmed-5027689
recordtype	oai_dc
spelling	pubmed-50276892016-10-01 The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer Esteban-Jurado, Clara Franch-Expósito, Sebastià Muñoz, Jenifer Ocaña, Teresa Carballal, Sabela López-Cerón, Maria Cuatrecasas, Miriam Vila-Casadesús, Maria Lozano, Juan José Serra, Enric Beltran, Sergi Brea-Fernández, Alejandro Ruiz-Ponte, Clara Castells, Antoni Bujanda, Luis Garre, Pilar Caldés, Trinidad Cubiella, Joaquín Balaguer, Francesc Castellví-Bel, Sergi Short Report Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 proteins and it is necessary to restore genome integrity by efficiently repairing damaged DNA. A link between FA genes in breast and ovarian cancer germline predisposition has been previously suggested. We selected 74 CRC patients from 40 unrelated Spanish families with strong CRC aggregation compatible with an autosomal dominant pattern of inheritance and without mutations in known hereditary CRC genes and performed germline DNA whole-exome sequencing with the aim of finding new candidate germline predisposition variants. After sequencing and data analysis, variant prioritization selected only those very rare alterations, producing a putative loss of function and located in genes with a role compatible with cancer. We detected an enrichment for variants in FA DNA damage repair pathway genes in our familial CRC cohort as 6 families carried heterozygous, rare, potentially pathogenic variants located in BRCA2/FANCD1, BRIP1/FANCJ, FANCC, FANCE and REV3L/POLZ. In conclusion, the FA DNA damage repair pathway may play an important role in the inherited predisposition to CRC. Nature Publishing Group 2016-10 2016-05-11 /pmc/articles/PMC5027689/ /pubmed/27165003 http://dx.doi.org/10.1038/ejhg.2016.44 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Esteban-Jurado, Clara Franch-Expósito, Sebastià Muñoz, Jenifer Ocaña, Teresa Carballal, Sabela López-Cerón, Maria Cuatrecasas, Miriam Vila-Casadesús, Maria Lozano, Juan José Serra, Enric Beltran, Sergi Brea-Fernández, Alejandro Ruiz-Ponte, Clara Castells, Antoni Bujanda, Luis Garre, Pilar Caldés, Trinidad Cubiella, Joaquín Balaguer, Francesc Castellví-Bel, Sergi
spellingShingle	Esteban-Jurado, Clara Franch-Expósito, Sebastià Muñoz, Jenifer Ocaña, Teresa Carballal, Sabela López-Cerón, Maria Cuatrecasas, Miriam Vila-Casadesús, Maria Lozano, Juan José Serra, Enric Beltran, Sergi Brea-Fernández, Alejandro Ruiz-Ponte, Clara Castells, Antoni Bujanda, Luis Garre, Pilar Caldés, Trinidad Cubiella, Joaquín Balaguer, Francesc Castellví-Bel, Sergi The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer
author_facet	Esteban-Jurado, Clara Franch-Expósito, Sebastià Muñoz, Jenifer Ocaña, Teresa Carballal, Sabela López-Cerón, Maria Cuatrecasas, Miriam Vila-Casadesús, Maria Lozano, Juan José Serra, Enric Beltran, Sergi Brea-Fernández, Alejandro Ruiz-Ponte, Clara Castells, Antoni Bujanda, Luis Garre, Pilar Caldés, Trinidad Cubiella, Joaquín Balaguer, Francesc Castellví-Bel, Sergi
author_sort	Esteban-Jurado, Clara
title	The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer
title_short	The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer
title_full	The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer
title_fullStr	The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer
title_full_unstemmed	The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer
title_sort	fanconi anemia dna damage repair pathway in the spotlight for germline predisposition to colorectal cancer
description	Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 proteins and it is necessary to restore genome integrity by efficiently repairing damaged DNA. A link between FA genes in breast and ovarian cancer germline predisposition has been previously suggested. We selected 74 CRC patients from 40 unrelated Spanish families with strong CRC aggregation compatible with an autosomal dominant pattern of inheritance and without mutations in known hereditary CRC genes and performed germline DNA whole-exome sequencing with the aim of finding new candidate germline predisposition variants. After sequencing and data analysis, variant prioritization selected only those very rare alterations, producing a putative loss of function and located in genes with a role compatible with cancer. We detected an enrichment for variants in FA DNA damage repair pathway genes in our familial CRC cohort as 6 families carried heterozygous, rare, potentially pathogenic variants located in BRCA2/FANCD1, BRIP1/FANCJ, FANCC, FANCE and REV3L/POLZ. In conclusion, the FA DNA damage repair pathway may play an important role in the inherited predisposition to CRC.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027689/
_version_	1613654726776193024

The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer

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