Skip to main content
Erschienen in: Medical Oncology 8/2019

01.08.2019 | Review Article

Functional coding and non-coding variants in human BRCA1 gene and their use in genetic screening

verfasst von: Gulten Tuncel, Mahmut Çerkez Ergören

Erschienen in: Medical Oncology | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Abstract

BRCA1 is involved in double-strand DNA damage repair pathways, and mutations in the gene are associated with hereditary breast and ovarian cancers. With great help of the development of high-throughput DNA sequencing techniques numerous single-nucleotide polymorphisms (SNPs) and insertion deletion (Indel) mutations are detected on both coding and non-coding/regulatory regions of the BRCA1. Mutations may cause pathogenic or benign changes on the protein function or affect its expression. In the last decade, use of genetic screening tests to detect mutations on such genes has become greatly popular. However, it is very important to know the effect of the detected mutations, which is mostly possible by the use of predictive softwares, and also the related family history to be able to correctly analyse the screening results and to inform the patient. Therefore, use of in silico and in vitro techniques to score the pathogenicity of detected variants on genes like BRCA1 is now of great importance. Otherwise, results obtained from screening tests and family history cannot be analysed precisely.
Literatur
1.
Zurück zum Zitat Campbell CD, Eichler EE. Properties and rates of germline mutations in humans. Trends Genet. 2013;29(10):575–84.CrossRef Campbell CD, Eichler EE. Properties and rates of germline mutations in humans. Trends Genet. 2013;29(10):575–84.CrossRef
2.
Zurück zum Zitat Griffiths AJ, et al. Somatic versus germinal mutation. An introduction to genetic analysis. Stuttgart: W. H. Freeman; 2000. Griffiths AJ, et al. Somatic versus germinal mutation. An introduction to genetic analysis. Stuttgart: W. H. Freeman; 2000.
3.
Zurück zum Zitat Wu J, Lu LY, Yu X. The role of BRCA1 in DNA damage response. Protein Cell. 2010;1(2):117–23.CrossRef Wu J, Lu LY, Yu X. The role of BRCA1 in DNA damage response. Protein Cell. 2010;1(2):117–23.CrossRef
4.
Zurück zum Zitat Petrucelli N, Daly MB, Feldman GL. Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2. Genet Med. 2010;12(5):245–59.CrossRef Petrucelli N, Daly MB, Feldman GL. Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2. Genet Med. 2010;12(5):245–59.CrossRef
5.
Zurück zum Zitat Lippi G, Mattiuzzi C, Montagnana M. BRCA population screening for predicting breast cancer: for or against? Ann Transl Med. 2017;5:13.CrossRef Lippi G, Mattiuzzi C, Montagnana M. BRCA population screening for predicting breast cancer: for or against? Ann Transl Med. 2017;5:13.CrossRef
8.
9.
Zurück zum Zitat Smigielski EM, et al. dbSNP: a database of single nucleotide polymorphisms. Nucleic Acids Res. 2000;28(1):352–5.CrossRef Smigielski EM, et al. dbSNP: a database of single nucleotide polymorphisms. Nucleic Acids Res. 2000;28(1):352–5.CrossRef
10.
Zurück zum Zitat Thery JC, et al. Contribution of bioinformatics predictions and functional splicing assays to the interpretation of unclassified variants of the BRCA genes. Eur J Hum Genet. 2011;19(10):1052–8.CrossRef Thery JC, et al. Contribution of bioinformatics predictions and functional splicing assays to the interpretation of unclassified variants of the BRCA genes. Eur J Hum Genet. 2011;19(10):1052–8.CrossRef
11.
Zurück zum Zitat Esposito MV, et al. A novel pathogenic BRCA1 splicing variant produces partial intron retention in the mature messenger RNA. Int J Mol Sci. 2016;17(12):2145.CrossRef Esposito MV, et al. A novel pathogenic BRCA1 splicing variant produces partial intron retention in the mature messenger RNA. Int J Mol Sci. 2016;17(12):2145.CrossRef
12.
Zurück zum Zitat López de Silanes I, Paz Quesada M, Esteller M. Aberrant regulation of messenger RNA 3 and M. Esteller, r Intron Retention. Cell Oncol. 2007;29(1):1–17.PubMedPubMedCentral López de Silanes I, Paz Quesada M, Esteller M. Aberrant regulation of messenger RNA 3 and M. Esteller, r Intron Retention. Cell Oncol. 2007;29(1):1–17.PubMedPubMedCentral
13.
Zurück zum Zitat Singh P, et al. Global changes in processing of mRNA 3′ untranslated regions characterize clinically distinct cancer subtypes. Cancer Res. 2009;69(24):9422–30.CrossRef Singh P, et al. Global changes in processing of mRNA 3′ untranslated regions characterize clinically distinct cancer subtypes. Cancer Res. 2009;69(24):9422–30.CrossRef
14.
Zurück zum Zitat Mao G, Pan X, Gu L. Evidence that a mutation in the MLH1 3′-untranslated region confers a mutator phenotype and mismatch repair deficiency in patients with relapsed leukemia. J Biol Chem. 2008;283(6):3211–6.CrossRef Mao G, Pan X, Gu L. Evidence that a mutation in the MLH1 3′-untranslated region confers a mutator phenotype and mismatch repair deficiency in patients with relapsed leukemia. J Biol Chem. 2008;283(6):3211–6.CrossRef
15.
Zurück zum Zitat Karbassi I, et al. A standardized DNA variant scoring system for pathogenicity assessments in mendelian disorders. Hum Mutat. 2016;37(1):127–34.CrossRef Karbassi I, et al. A standardized DNA variant scoring system for pathogenicity assessments in mendelian disorders. Hum Mutat. 2016;37(1):127–34.CrossRef
16.
Zurück zum Zitat Dorairaj JJ, et al. A germline mutation in the BRCA1 3′ UTR predicts stage IV breast cancer. BMC Cancer. 2014;14:421.CrossRef Dorairaj JJ, et al. A germline mutation in the BRCA1 3′ UTR predicts stage IV breast cancer. BMC Cancer. 2014;14:421.CrossRef
17.
Zurück zum Zitat Brewster BL, et al. Identification of fifteen novel germline variants in the BRCA1 3′ UTR reveals a variant in a breast cancer case that introduces a functional miR-103 target site. Hum Mutat. 2012;33(12):1665–75.CrossRef Brewster BL, et al. Identification of fifteen novel germline variants in the BRCA1 3′ UTR reveals a variant in a breast cancer case that introduces a functional miR-103 target site. Hum Mutat. 2012;33(12):1665–75.CrossRef
18.
Zurück zum Zitat Gochhait S, et al. Implication of BRCA2-26G>A 5′ untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53 codon 72 Arg > Pro polymorphism. Breast Cancer Res. 2007;9(5):R71.CrossRef Gochhait S, et al. Implication of BRCA2-26G>A 5′ untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53 codon 72 Arg > Pro polymorphism. Breast Cancer Res. 2007;9(5):R71.CrossRef
19.
Zurück zum Zitat Evans DGR, et al. A dominantly inherited 5′ UTR variant causing methylation-associated silencing of BRCA1 as a cause of breast and ovarian cancer. Am J Hum Genet. 2018;103(2):213–20.CrossRef Evans DGR, et al. A dominantly inherited 5′ UTR variant causing methylation-associated silencing of BRCA1 as a cause of breast and ovarian cancer. Am J Hum Genet. 2018;103(2):213–20.CrossRef
20.
Zurück zum Zitat Sim NL, et al. SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res. 2012;40:W452–7.CrossRef Sim NL, et al. SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res. 2012;40:W452–7.CrossRef
21.
Zurück zum Zitat Zick A, et al. A BRCA1 frame shift mutation in women of Kurdish Jewish descent. Open Med J. 2015;2:31–6.CrossRef Zick A, et al. A BRCA1 frame shift mutation in women of Kurdish Jewish descent. Open Med J. 2015;2:31–6.CrossRef
22.
Zurück zum Zitat Benson JM, Therrell BL Jr. History and current status of newborn screening for hemoglobinopathies. Semin Perinatol. 2010;34(2):134–44.CrossRef Benson JM, Therrell BL Jr. History and current status of newborn screening for hemoglobinopathies. Semin Perinatol. 2010;34(2):134–44.CrossRef
23.
Zurück zum Zitat Kaplan F. Tay–Sachs disease carrier screening: a model for prevention of genetic disease. Genet Test. 1998;2(4):271–92.CrossRef Kaplan F. Tay–Sachs disease carrier screening: a model for prevention of genetic disease. Genet Test. 1998;2(4):271–92.CrossRef
24.
Zurück zum Zitat Bozkurt G. Results from the north cyprus thalassemia prevention program. Hemoglobin. 2007;31(2):257–64.CrossRef Bozkurt G. Results from the north cyprus thalassemia prevention program. Hemoglobin. 2007;31(2):257–64.CrossRef
25.
Zurück zum Zitat Lynch J, Venne V, Berse B. Genetic tests to identify risk for breast cancer. Semin Oncol Nurs. 2015;31(2):100–7.CrossRef Lynch J, Venne V, Berse B. Genetic tests to identify risk for breast cancer. Semin Oncol Nurs. 2015;31(2):100–7.CrossRef
26.
Zurück zum Zitat Cline MS, et al. BRCA challenge: BRCA exchange as a global resource for variants in BRCA1 and BRCA2. PLoS Genet. 2018;14(12):e1007752.CrossRef Cline MS, et al. BRCA challenge: BRCA exchange as a global resource for variants in BRCA1 and BRCA2. PLoS Genet. 2018;14(12):e1007752.CrossRef
Metadaten
Titel
Functional coding and non-coding variants in human BRCA1 gene and their use in genetic screening
verfasst von
Gulten Tuncel
Mahmut Çerkez Ergören
Publikationsdatum
01.08.2019
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 8/2019
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-019-1294-9

Weitere Artikel der Ausgabe 8/2019

Medical Oncology 8/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.