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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 21853naa a2206565 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:142209073 | |
| 003 | SwePub | |
| 008 | 240701s2019 | |||||||||||000 ||eng| | |
| 009 | oai:DiVA.org:uu-397654 | |
| 009 | oai:lup.lub.lu.se:c1cc6d81-4544-45eb-b7dc-dd5e1a5e72ba | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1422090732 URI |
| 024 | 7 | a https://doi.org/10.1038/s41523-019-0127-52 DOI |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3976542 URI |
| 024 | 7 | a https://lup.lub.lu.se/record/c1cc6d81-4544-45eb-b7dc-dd5e1a5e72ba2 URI |
| 040 | a (SwePub)kid (SwePub)uud (SwePub)lu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Figlioli, Gu IFOM FIRC Inst Mol Oncol, Genome Diagnost Program, Milan, Italy,IFOM - The FIRC Institute of Molecular Oncology4 aut |
| 245 | 1 0 | a The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer |
| 264 | c 2019-11-01 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2019 |
| 500 | a For complete list of authors see http://dx.doi.org/10.1038/s41523-019-0127-5 | |
| 520 | a Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
| 653 | a arginine | |
| 653 | a arginine 658 | |
| 653 | a ATM protein | |
| 653 | a BRCA1 protein | |
| 653 | a BRCA2 protein | |
| 653 | a butadiene diepoxide | |
| 653 | a checkpoint kinase 2 | |
| 653 | a olaparib | |
| 653 | a partner and localizer of BRCA2 | |
| 653 | a unclassified drug | |
| 653 | a Article | |
| 653 | a ATM protein gene | |
| 653 | a BRCA1 protein gene | |
| 653 | a BRCA2 protein gene | |
| 653 | a cell survival | |
| 653 | a checkpoint kinase 2 gene | |
| 653 | a chromosomal instability | |
| 653 | a chromosome fragility | |
| 653 | a controlled study | |
| 653 | a FANCM gene | |
| 653 | a female | |
| 653 | a gene | |
| 653 | a gene expression | |
| 653 | a gene mutation | |
| 653 | a genotype | |
| 653 | a human | |
| 653 | a informed consent | |
| 653 | a major clinical study | |
| 653 | a mRNA expression level | |
| 653 | a partner and localizer of BRCA2 gene | |
| 653 | a phenotype | |
| 653 | a priority journal | |
| 653 | a risk factor | |
| 653 | a sensitivity analysis | |
| 653 | a survival rate | |
| 653 | a triple negative breast cancer | |
| 653 | a Western blotting | |
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| 700 | 1 | a Thorne, H4 aut |
| 700 | 1 | a Armitage, S4 aut |
| 700 | 1 | a Arnold, L4 aut |
| 700 | 1 | a Kefford, R4 aut |
| 700 | 1 | a Kirk, J4 aut |
| 700 | 1 | a Rickard, E4 aut |
| 700 | 1 | a Bastick, P4 aut |
| 700 | 1 | a Beesley, J4 aut |
| 700 | 1 | a Hayward, N4 aut |
| 700 | 1 | a Spurdle, A4 aut |
| 700 | 1 | a Walker, L4 aut |
| 700 | 1 | a Beilby, J4 aut |
| 700 | 1 | a Saunders, C4 aut |
| 700 | 1 | a Bennett, I4 aut |
| 700 | 1 | a Blackburn, A4 aut |
| 700 | 1 | a Bogwitz, M4 aut |
| 700 | 1 | a Gaff, C4 aut |
| 700 | 1 | a Lindeman, G4 aut |
| 700 | 1 | a Pachter, N4 aut |
| 700 | 1 | a Scott, C4 aut |
| 700 | 1 | a Sexton, A4 aut |
| 700 | 1 | a Visvader, J4 aut |
| 700 | 1 | a Taylor, J4 aut |
| 700 | 1 | a Winship, I4 aut |
| 700 | 1 | a Brennan, M4 aut |
| 700 | 1 | a Brown, M4 aut |
| 700 | 1 | a French, J4 aut |
| 700 | 1 | a Edwards, S4 aut |
| 700 | 1 | a Burgess, M4 aut |
| 700 | 1 | a Burke, J4 aut |
| 700 | 1 | a Patterson, B4 aut |
| 700 | 1 | a Butow, P4 aut |
| 700 | 1 | a Culling, B4 aut |
| 700 | 1 | a Caldon, L4 aut |
| 700 | 1 | a Callen, D4 aut |
| 700 | 1 | a Chauhan, D4 aut |
| 700 | 1 | a Eisenbruch, M4 aut |
| 700 | 1 | a Heiniger, L4 aut |
| 700 | 1 | a Chauhan, M4 aut |
| 700 | 1 | a Christian, A4 aut |
| 700 | 1 | a Dixon, J4 aut |
| 700 | 1 | a Kidd, A4 aut |
| 700 | 1 | a Cohen, P4 aut |
| 700 | 1 | a Colley, A4 aut |
| 700 | 1 | a Fenton, G4 aut |
| 700 | 1 | a Crook, A4 aut |
| 700 | 1 | a Dickson, R4 aut |
| 700 | 1 | a Field, M4 aut |
| 700 | 1 | a Cui, J4 aut |
| 700 | 1 | a Cummings, M4 aut |
| 700 | 1 | a Dawson, SJ4 aut |
| 700 | 1 | a DeFazio, A4 aut |
| 700 | 1 | a Delatycki, M4 aut |
| 700 | 1 | a Dudding, T4 aut |
| 700 | 1 | a Edkins, T4 aut |
| 700 | 1 | a Farshid, G4 aut |
| 700 | 1 | a Flanagan, J4 aut |
| 700 | 1 | a Fong, P4 aut |
| 700 | 1 | a Forrest, L4 aut |
| 700 | 1 | a Gallego-Ortega, D4 aut |
| 700 | 1 | a George, P4 aut |
| 700 | 1 | a Gill, G4 aut |
| 700 | 1 | a Kollias, J4 aut |
| 700 | 1 | a Haan, E4 aut |
| 700 | 1 | a Hart, S4 aut |
| 700 | 1 | a Jenkins, M4 aut |
| 700 | 1 | a Hunt, C4 aut |
| 700 | 1 | a Lakhani, S4 aut |
| 700 | 1 | a Lipton, L4 aut |
| 700 | 1 | a Lobb, L4 aut |
| 700 | 1 | a Mann, G4 aut |
| 700 | 1 | a McLachlan, SA4 aut |
| 700 | 1 | a O'Connell, S4 aut |
| 700 | 1 | a O'Sullivan, S4 aut |
| 700 | 1 | a Pieper, E4 aut |
| 700 | 1 | a Robinson, B4 aut |
| 700 | 1 | a Saunus, J4 aut |
| 700 | 1 | a Scott, E4 aut |
| 700 | 1 | a Shelling, A4 aut |
| 700 | 1 | a Williams, R4 aut |
| 700 | 1 | a Young, MAu Genome One, Darlinghurst, NSW, Australia4 aut |
| 710 | 2 | a IFOM FIRC Inst Mol Oncol, Genome Diagnost Program, Milan, Italyb IFOM - The FIRC Institute of Molecular Oncology4 org |
| 773 | 0 | t NPJ breast cancerd : Springer Science and Business Media LLCg 5, s. 38-q 5<38-x 2374-4677 |
| 856 | 4 | u https://www.nature.com/articles/s41523-019-0127-5.pdf |
| 856 | 4 | u https://doi.org/10.1038/s41523-019-0127-5y Fulltext |
| 856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1374882/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
| 856 | 4 | u http://dx.doi.org/10.1038/s41523-019-0127-5x freey FULLTEXT |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:142209073 |
| 856 | 4 8 | u https://doi.org/10.1038/s41523-019-0127-5 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-397654 |
| 856 | 4 8 | u https://lup.lub.lu.se/record/c1cc6d81-4544-45eb-b7dc-dd5e1a5e72ba |
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