Abstract
Fanconi anemia is a genetically heterogeneous autosomal recessive disorder characterized by development abnormalities, bone marrow failure, and childhood cancers. Compelling evidence indicates a common genetic basis for FA and breast/ovarian cancer susceptibility. Recently, biallelic germ-line mutations in SLX4 have been demonstrated to cause a previously unknown FA subtype (FA-P). We address the role of SLX4/FANCP in breast/ovarian cancer susceptibility by conducting a comprehensive mutation scanning in 486 index cases from non-BRCA1/BRCA2 multiple-case breast and/or ovarian cancer families (non-BRCA1/2 families) from Spain. We detected one unequivocal loss-of-function mutation (p.Glu1517X). In addition, one missense change (p.Arg372Trp) predicted to be pathogenic by in silico analysis co-segregates with disease in one family. Overall, the study indicates that SLX4 mutation screening will have a very low impact (if any) in the genetic counseling of non-BRCA1/2 families.
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Acknowledgements
We thank the patients whose participation made this project possible. We thank Paula Diaque for technical assistance. This study was supported by Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS) Research Grants 09/00859, and Fundación Mutua Madrileña (FMM) Research Grant FMM-08, to MH. Xunta de Galicia (10PXIB 9101297PR) and Fundación Mutua Madrileña (FMM-10) to AV. Red Temática de Investigación Cooperativa en Cáncer; Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RETICC 06/0020/0021) supported PG, AR, PPS, EDR, TC, and MdH. None of these study sponsors had any role in study design, in the collection, analysis, and interpretation of data; in the writing of the report; and/or in the decision to submit the paper for publication.
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de Garibay, G., Díaz, A., Gaviña, B. et al. Low prevalence of SLX4 loss-of-function mutations in non-BRCA1/2 breast and/or ovarian cancer families. Eur J Hum Genet 21, 883–886 (2013). https://doi.org/10.1038/ejhg.2012.268
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DOI: https://doi.org/10.1038/ejhg.2012.268
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