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Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer

  • Authors:
    • Hong Zhang
    • Linsen Li
    • Yuxia Wang
    • C. Cameron Yin
    • Yuntao Xie
    • Xijuan Liu
    • Huirong Ding
    • Zhihua Tian
    • Jing Shen
    • Long He
    • Miaoran Xia
    • Xi Ma
    • Lina Wu
  • View Affiliations / Copyright

    Affiliations: Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, P.R. China, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, P.R. China, Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, P.R. China, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5839-5844
    |
    Published online on: September 19, 2017
       https://doi.org/10.3892/ol.2017.7003
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Abstract

Breast cancer 1 (BRCA1) is one of the most common tumor suppressor genes in breast cancer. The BRCT domain of BRCA1 has been shown to have a critical role in tumor suppression. In a previous study, two de novo BRCT missense mutations of BRCA1, G1763V and L1786P were identified from Chinese females with familial breast cancer. In the present study, the function of these two novel mutations were assessed by bioinformatics analysis and a series of experiments investigating cell proliferation, cell cycle and chemotherapy combination. Although bioinformatics analysis indicated that the mutants may be deleterious, a series of experiments revealed that the two mutants significantly reduced the growth and increased cell apoptosis similar to the function of BRCA1 wild type. Furthermore, no synergistic effect between the Olaparib and BRCA1 mutation was noted on cell apoptosis. These results demonstrated that these two mutations did not affect the tumor suppressor function of BRCA1. It was concluded that not all BRCA1 missense mutations are pathogenic and that any new BRCA1 mutation should be assessed for its effect on the tumor suppressor function of BRCA1.
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1 

Welcsh PL, Owens KN and King MC: Insights into the functions of BRCA1 and BRCA2. Trends Genet. 16:69–74. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Bergman A, Flodin A, Engwall Y, Arkblad EL, Berg K and Nordling M, Martinsson T, Wahlström J, Karlsson P and Nordling M: A high frequency of germline BRCA1/2 mutations in western Sweden detected with complementary screening techniques. Fam Cancer. 4:89–96. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Zhang J, Pei R, Pang Z, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B and Xie Y: Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer. Breast Cancer Res Treat. 132:421–428. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Mullan PB, Quinn JE and Harkin DP: The role of BRCA1 in transcriptional regulation and cell cycle control. Oncogene. 25:5854–5863. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Baer R and Ludwig T: The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E3 ligase activity. Curr Opin Genet Dev. 12:86–91. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Moynahan ME and Jasin M: Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol. 11:196–207. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Shakya R, Reid LJ, Reczek CR, Cole F, Egli D, Lin CS, deRooij DG, Hirsch S, Ravi K, Hicks JB, et al: BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science. 334:525–528. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Linger RJ and Kruk PA: BRCA1 16 years later: Risk-associated BRCA1 mutations and their functional implications. FEBS J. 277:3086–3096. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Konishi H, Mohseni M, Tamaki A, Garay JP, Croessmann S, Karnan S, Ota A, Wong HY, Konishi Y, Karakas B, et al: Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells. Proc Natl Acad Sci USA. 108:17773–17778. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Figge MA and Blankenship L: Missense mutations in the BRCT domain of BRCA-1 from high-risk women frequently perturb strongly hydrophobic amino acids conserved among mammals. Cancer Epidemiol Biomarkers Prev. 13:1037–1041. 2004.PubMed/NCBI

11 

Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ and Goldgar DE: A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet. 81:873–883. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Foulkes WD and Shuen AY: In brief: BRCA1 and BRCA2. J Pathol. 230:347–349. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Pohlreich P, Zikan M, Stribrna J, Kleibl Z, Janatova M, Kotlas J, Zidovska J, Novotny J, Petruzelka L, Szabo C and Matous B: High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area. Breast Cancer Res. 7:R728–R736. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J, Roach KC, Mandell J, Lee MK, Ciernikova S, et al: Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 295:1379–1388. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Kwong A, Ng EK, Tang EY, Wong CL, Law FB, Leung CP, Chan A, Cheung MT, To MY, Ma ES, et al: A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer. Fam Cancer. 10:233–237. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Neamatzadeh H, Shiryazdi SM and Kalantar SM: BRCA1 and BRCA2 mutations in Iranian breast cancer patients: A systematic review. J Res Med Sci. 20:284–293. 2015.PubMed/NCBI

18 

Moynahan ME and Jasin M: Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol. 11:196–207. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Huen MS, Sy SM and Chen J: BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol. 11:138–148. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Satoh MS and Lindahl T: Role of poly(ADP-ribose) formation in DNA repair. Nature. 356:356–358. 1992. View Article : Google Scholar : PubMed/NCBI

21 

Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, et al: Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 361:123–134. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Guha M: PARP inhibitors stumble in breast cancer. Nat Biotechnol. 29:373–374. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Lee JM, Ledermann JA and Kohn EC: PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol. 25:32–40. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Bixel K and Hays JL: Olaparib in the management of ovarian cancer. Pharmgenomics Pers Med. 8:127–135. 2015.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang H, Li L, Wang Y, Yin CC, Xie Y, Liu X, Ding H, Tian Z, Shen J, He L, He L, et al: Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer. Oncol Lett 14: 5839-5844, 2017.
APA
Zhang, H., Li, L., Wang, Y., Yin, C.C., Xie, Y., Liu, X. ... Wu, L. (2017). Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer. Oncology Letters, 14, 5839-5844. https://doi.org/10.3892/ol.2017.7003
MLA
Zhang, H., Li, L., Wang, Y., Yin, C. C., Xie, Y., Liu, X., Ding, H., Tian, Z., Shen, J., He, L., Xia, M., Ma, X., Wu, L."Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer". Oncology Letters 14.5 (2017): 5839-5844.
Chicago
Zhang, H., Li, L., Wang, Y., Yin, C. C., Xie, Y., Liu, X., Ding, H., Tian, Z., Shen, J., He, L., Xia, M., Ma, X., Wu, L."Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer". Oncology Letters 14, no. 5 (2017): 5839-5844. https://doi.org/10.3892/ol.2017.7003
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang H, Li L, Wang Y, Yin CC, Xie Y, Liu X, Ding H, Tian Z, Shen J, He L, He L, et al: Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer. Oncol Lett 14: 5839-5844, 2017.
APA
Zhang, H., Li, L., Wang, Y., Yin, C.C., Xie, Y., Liu, X. ... Wu, L. (2017). Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer. Oncology Letters, 14, 5839-5844. https://doi.org/10.3892/ol.2017.7003
MLA
Zhang, H., Li, L., Wang, Y., Yin, C. C., Xie, Y., Liu, X., Ding, H., Tian, Z., Shen, J., He, L., Xia, M., Ma, X., Wu, L."Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer". Oncology Letters 14.5 (2017): 5839-5844.
Chicago
Zhang, H., Li, L., Wang, Y., Yin, C. C., Xie, Y., Liu, X., Ding, H., Tian, Z., Shen, J., He, L., Xia, M., Ma, X., Wu, L."Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer". Oncology Letters 14, no. 5 (2017): 5839-5844. https://doi.org/10.3892/ol.2017.7003
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