dc.contributor.author |
Castells-Roca, Laia |
dc.contributor.author |
Gutiérrez-Enríquez, Sara |
dc.contributor.author |
Bonache, Sandra |
dc.contributor.author |
Bogliolo, Massimo |
dc.contributor.author |
Carrasco, E. |
dc.contributor.author |
Aza-Carmona, Miriam |
dc.contributor.author |
Montalban, G. |
dc.contributor.author |
Muñoz-Subirana, N. |
dc.contributor.author |
Pujol, Roser |
dc.contributor.author |
Cruz Zambrano, Cristina |
dc.contributor.author |
Llop-Guevara, A. |
dc.contributor.author |
Ramírez de Haro, Ma. José |
dc.contributor.author |
Saura, Cristina |
dc.contributor.author |
Lasa, Adriana |
dc.contributor.author |
Serra, V. |
dc.contributor.author |
Diez, Orland |
dc.contributor.author |
Balmaña Gelpí, Judith |
dc.contributor.author |
Surrallés i Calonge, Jordi |
dc.contributor.author |
Universitat Autònoma de Barcelona |
dc.date |
2021 |
dc.identifier |
https://ddd.uab.cat/record/269625 |
dc.identifier |
urn:10.1038/s41523-021-00322-9 |
dc.identifier |
urn:oai:ddd.uab.cat:269625 |
dc.identifier |
urn:scopus_id:85114769661 |
dc.identifier |
urn:articleid:23744677v7n1p117 |
dc.identifier |
urn:pmid:34504103 |
dc.identifier |
urn:pmc-uid:8429460 |
dc.identifier |
urn:pmcid:PMC8429460 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:8429460 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Instituto de Salud Carlos III CP16/ 00034 |
dc.relation |
Instituto de Salud Carlos III CPII19/00033 |
dc.relation |
Instituto de Salud Carlos III PI12/02606 |
dc.relation |
Instituto de Salud Carlos III PI16/01218 |
dc.relation |
Instituto de Salud Carlos III PI17/01080 |
dc.relation |
Instituto de Salud Carlos III PI19/01303 |
dc.relation |
Instituto de Salud Carlos III ACCI-U705/U745-2018 |
dc.relation |
European Commission. Horizon 2020 Marie Skłodowska-Curie 665919 |
dc.relation |
European Commission HEALTH-F5-2012-305421 |
dc.relation |
Ministerio de Ciencia, Innovación y Universidades CB06/07/0023 MCI |
dc.relation |
Ministerio de Ciencia, Innovación y Universidades RTI2018-098419-B-I00 MCI |
dc.relation |
Ministerio de Sanidad FANCOSTEM |
dc.relation |
Ministerio de Sanidad FANCOLEN |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2017 SGR 540 |
dc.relation |
NPJ breast cancer ; Vol. 7 Núm. 1 (december 2021), p. 117 |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
dc.title |
Clinical consequences of BRCA2 hypomorphism |
dc.type |
Article |
dc.description.abstract |
Altres ajuts: Asociación Española contra el Cáncer (LABAE16020PORTT) |
dc.description.abstract |
Altres ajuts: Asociación Española contra el Cáncer (ERAPERMED2019-215) |
dc.description.abstract |
The tumor suppressor FANCD1/BRCA2 is crucial for DNA homologous recombination repair (HRR). BRCA2 biallelic pathogenic variants result in a severe form of Fanconi anemia (FA) syndrome, whereas monoallelic pathogenic variants cause mainly hereditary breast and ovarian cancer predisposition. For decades, the co-occurrence in trans with a clearly pathogenic variant led to assume that the other allele was benign. However, here we show a patient with biallelic BRCA2 (c.1813dup and c.7796 A > G) diagnosed at age 33 with FA after a hypertoxic reaction to chemotherapy during breast cancer treatment. After DNA damage, patient cells displayed intermediate chromosome fragility, reduced survival, cell cycle defects, and significantly decreased RAD51 foci formation. With a newly developed cell-based flow cytometric assay, we measured single BRCA2 allele contributions to HRR, and found that expression of the missense allele in a BRCA2 KO cellular background partially recovered HRR activity. Our data suggest that a hypomorphic BRCA2 allele retaining 37-54% of normal HRR function can prevent FA clinical phenotype, but not the early onset of breast cancer and severe hypersensitivity to chemotherapy. |