Skip to main content

Detection of a novel mutation in exon 20 of the BRCA1 gene

An Erratum to this article was published on 15 March 2014


Hereditary breast cancer constitutes 5–10% of all breast cancer cases. Inherited mutations in the BRCA1 and BRCA2 tumor-suppressor genes account for the majority of hereditary breast cancer cases. The BRCA1 C-terminal region (BRCT) has a functional duplicated globular domain, which helps with DNA damage repair and cell cycle checkpoint protein control. More than 100 distinct BRCA1 missense variants with structural and functional effects have been documented within the BRCT domain. Interpreting the results of mutation screening of tumor-suppressor genes that can have high-risk susceptibility mutations is increasingly important in clinical practice. This study includes a novel mutation, p.His1746 Pro (c.5237A>C), which was found in BRCA1 exon 20 of a breast cancer patient. In silico analysis suggests that this mutation could alter the stability and orientation of the BRCT domain and the differential binding of the BACH1 substrate.



BRCA1-associated C-terminal helicase


Breast Cancer Information Core


breast cancer gene one


BRCA 1 C-terminal domain


free energy change


Human Gene Mutation Database


Human Genome Variation Society


Mendelian Inheritance in Man


National Center for Biotechnology Information


ovarian cancer


root mean-square deviation


  1. Gajalakshmi, C.K., Shanta, V., Swaminathan, R., Sankaranarayanan, R. and Black, R.J. A population-based survival study on female breast cancer in Madras, India. Br. J. Cancer 75 (1997) 771–775.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  2. Pestonjamasp, P.H. and Mittra, I. Analysis of BRCA1 involvement in breast cancer in Indian women. J. Biosci. 25 (2000) 19–23.

    PubMed  Article  CAS  Google Scholar 

  3. Murthy, N.S., Chaudhry, K., Nadayil, D., Agarwal, U.K. and Saxena, S. Changing trends in incidence of breast cancer: Indian scenario. Ind. J. Cancer 46 (2009) 73–74.

    Article  CAS  Google Scholar 

  4. Armaou, S., Pertesi, M., Fostira, F., Thodi, G., Athanasopoulos, P.S., Kamakari, S., Athanasiou, A., Gogas, H., Yannoukakos, D., Fountzilas, G. and Konstantopoulou, I. Contribution of BRCA1 germ-line mutations to breast cancer in Greece: a hospital-based study of 987 unselected breast cancer cases. Br. J. Cancer 101 (2009) 32–37.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  5. Newman, B., Austin, M.A., Lee, M. and King, M.C. Inheritance of human breast cancer: evidence for autosomal dominant transmission in high-risk families. Proc. Natl. Acad. Sci. USA 85 (1988) 3044–3048.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  6. Begg, C.B., Haile, R.W., Borg, A., Malone, K.E., Concannon, P., Thomas, D.C., Langholz, B., Bernstein, L., Olsen, J.H., Lynch, C.F., Anton-Culver, H., Capanu, M., Liang, X., Hummer A.J., Sima, C. and Bernstein, J.L. Variation of breast cancer risk among BRCA1/2carriers. JAMA 299 (2008) 194–201.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  7. Stratton, M.R. and Rahman, N. The emerging landscape of breast cancer susceptibility. Nat. Genet. 40 (2008) 17–22.

    PubMed  Article  CAS  Google Scholar 

  8. Rosen, E.M., Fan, S., Pestell, R.G. and Goldberg, I.D. BRCA1 gene in breast cancer. J. Cell Physiol. 196 (2003) 19–41.

    PubMed  Article  CAS  Google Scholar 

  9. Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P.A., Harshman, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, L.M., Ding, W., Bell, R., Rosenthal, J., Hussey, C., Tran, T., Melody, M., Frye, C., Hattier, T. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266 (1994) 66–71.

    PubMed  Article  CAS  Google Scholar 

  10. Korlimarla, A., Bhandary, L., Prabhu, J.S., Shankar, H., Sankaranarayanan, H., Kumar, P., Remacle, J., Natarajan, D. and Sridhar, T.S. Identification of a non-canonical nuclear localization signal (NLS) in BRCA1 that could mediate nuclear localization of splice variants lacking the classical NLS. Cell. Mol. Biol. Lett. 18 (2013) 284–296.

    PubMed  Article  CAS  Google Scholar 

  11. Huen, M.S., Sy, S.M. and Chen, J. BRCA1 and its toolbox for the maintenance of genome integrity. Nat. Rev. Mol. Cell Biol. 11 (2010) 138–148.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  12. O’Donovan, P.J. and Livingston, D.M. BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis 31 (2010) 961–967.

    PubMed  Article  CAS  Google Scholar 

  13. Yu, X., Chini, C.C., He, M., Mer, G. and Chen, J. The BRCT domain is a phospho-protein binding domain. Science 302 (2003) 639–642.

    PubMed  Article  CAS  Google Scholar 

  14. Chakraborty, A., Mukhopadhyay, A., Bhattacharyya, D., Bose C.K., Choudhuri, K., Mukhopadhyay, S. and Basak, J. Frequency of 5382insC mutation of BRCA1 gene among breast cancer patients: an experience from Eastern India. Fam. Cancer 12 (2013) 489–495.

    PubMed  Article  CAS  Google Scholar 

  15. Miller, S.S., Dykes, D.D. and Polesky, H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16 (1988) 12152.

    Google Scholar 

  16. Dufloth, R.M, Carvalho, S., Heinrich, J.K., Shinzato, J.Y., Santos C.C., Zeferino, L.C. and Schmitt, F. Analysis of BRCA1 and BRCA2 mutations in Brazilian breast cancer patients with positive family history. Sao Paulo Med. J. 123 (2005) 192–197.

    PubMed  Article  Google Scholar 

  17. Trott, O. and Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31 (2010) 455–461.

    PubMed Central  PubMed  CAS  Google Scholar 

  18. Williams, R.S. and Glover, J.N. Structural consequences of a cancer-causing BRCA1-BRCT missense mutation. J. Biol. Chem. 278 (2003) 2630–2635.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Jayasri Basak.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chakraborty, A., Katarkar, A., Chaudhuri, K. et al. Detection of a novel mutation in exon 20 of the BRCA1 gene. Cell Mol Biol Lett 18, 631–638 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Key words

  • Breast cancer
  • BRCA1
  • BRCT repeat
  • BACH1
  • Cancer predisposition
  • DNA sequencing
  • Docking
  • Exon 20
  • In silico analysis
  • Missense mutation