BRCA mutations: is everything said?
Mutations in the BRCA1 and BRCA2 genes constitute a risk factor for breast cancer development. BRCA mutation research has been an active field since the discovery of the genes, and new mutations in both genes are constantly described and classified according to several systems.
We intend to provide an overview of the current state of BRCA1 and BRCA2 mutation description and classification. We wanted to know whether there was a trend towards a more frequently described mutation type and what the proportion of pathogenic mutations was.
We found that, although new mutations are described each year as reflected in current database records, very few of them are reported in papers. Classification systems are highly heterogeneous and a consensus among them is still under development. Regarding their function, a large number of mutations are yet to be analyzed, a very complex task, due to the great number of possible variations and their diverse effect in the BRCA gene functions. After individual analysis, many variants of unknown significance turn out to be pathogenic, and many can disrupt interactions with other proteins involved in mechanisms such as DNA damage repair pathways. Recent data suggest that looking for mutation patterns or combinations would shed a wider light on BRCA-derived cancer susceptibility in the upcoming years.
KeywordsBreast cancer risk BRCA1 BRCA2 Mutation Complex traits
This study was funded by DGAPA-PAPIIT, Universidad Nacional Autónoma de México with Grant Number IA201216, awarded to E.L-U. and grant number IN207216, awarded to C.P-P.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 1.BIC Consortium (1995) Breast cancer information core. https://research.nhgri.nih.govprojectsbic
- 4.Antonarakis SE (1998) Recommendations for a nomenclature system for human gene mutations. Hum Mutat 11:1–3. https://doi.org/10.1002/(SICI)1098-1004(1998)11:1%3C1::AID-HUMU1%3E3.0.CO;2-O CrossRefGoogle Scholar
- 9.Chenevix-Trench G, Milne RL, Antoniou AC et al (2007) An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). Breast Cancer Res 9:104. https://doi.org/10.1186/bcr1670 CrossRefGoogle Scholar
- 10.Spurdle AB, Healey S, Devereau A et al (2012) ENIGMA—evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes. Hum Mutat 33:2–7. https://doi.org/10.1002/humu.21628 CrossRefGoogle Scholar
- 12.2006 Human Variome Project, Appelbe W, Auerbach AD et al (2007) Recommendations of the 2006 human variome project meeting. In: Nat. Genet. pp 433–436Google Scholar
- 14.Puget N, Torchard D, Serova-Sinilnikova OM et al (1997) A 1-kb Alu-mediated germ-line deletion removing BRCA1 exon 17. Cancer Res 57:828–831Google Scholar
- 17.Szabo CI, King MC (1997) Population genetics of BRCA1 and BRCA2. Am J Hum Genet 60:1013–1020Google Scholar
- 22.Maillet P, Chappuis PO, Khoshbeen-Boudal M et al (2006) Twenty-three novel BRCA1 and BRCA2 sequence variations identified in a cohort of Swiss breast and ovarian cancer families. Cancer Genet Cytogenet 169:62–68. https://doi.org/10.1016/j.cancergencyto.2006.03.010 CrossRefGoogle Scholar
- 32.Di Giacomo D, Gaildrat P, Abuli A et al (2013) Functional Analysis of a Large set of BRCA2exon 7 variants highlights the predictive value of hexamer scores in detecting alterations of exonic splicing regulatory elements. Hum Mutat 34:1547–1557. https://doi.org/10.1002/humu.22428 CrossRefGoogle Scholar