Volume 26, Issue 8 (Nov 2019)                   JSSU 2019, 26(8): 733-739 | Back to browse issues page


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miresmaeili S M, kalantar S M. Detection of a novel mutations in Exon 11 of BRCA1 gene in the patients with hereditary breast cancer. JSSU. 2019; 26 (8) :733-739
URL: http://jssu.ssu.ac.ir/article-1-4669-en.html
Abstract:   (175 Views)
Introduction: Breast cancer is the most common malignancy in women worldwide. BRCA1 is a tumor suppressor gene that is involved in DNA-damage repair. One of the significant risk factors of breast cancer is the family history. BRCA1 gene consists of 24 exons that encode a protein with 1863 amino acids. Exon 11 is the largest exons and most of the disease-linked mutations have been found in it. Inherited mutations in the BRCA1 gene are constituted for the major hereditary breast cancer cases. Deficiency in BRCA1 gene was considered to be a high risk in the families with breast cancer. The goal of this study was to evalute mutation in BRCA1 gene in the patients with breast cancer.
Methods: In this study, blood samples were collected from 200 breast cancer patients. 40 patients suffer from hereditary breast cancer, after DNA extraction, exon 11 of BRCA1 genes were evaluated by PCR-SSCP technique followed by direct sequencing and the result of the changes was evaluated by in silico analysis.
Results: The samples, showing mobility shift on SSCP analysis, were used for direct DNA sequencing, two new missense mutations c.3059C>T (p.Pro1020Leu) and (p.Thr1025Ile) c.3074C>T were detected in the patients with hereditary breast cancer. In silico analysis on protein function revealed that the mutation c.3074C>T effected on protein structure and predicted to be possibly damaging.
Conclusion: Screening of the BRCA1 gene mutation can help to manage the treatment of the patients and their families. Therefore, for families exposed to cancer, genetic screening can help family members know if they need tests to look for cancer early, or if they should take steps to reduce their risk.
Full-Text [PDF 718 kb]   (85 Downloads)    
Type of Study: Original article | Subject: Genetics
Received: 2018/08/16 | Accepted: 2018/10/13

References
0.  
1. 1- Miki Y, Swensen J, Shattuck-Eidens D, Futreal P, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Sci 1994; 266(5182): 66-71.
2. 2- Li ML, A.Greenberg. R. Links between genome integrity and BRCA1 tumor suppression. Trends Biochem Sci 2012; 37(10): 418-24.
3. 3- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58(2): 71-96.
4. 4- Morris JR, Pangon L, Boutell C, Katagiri T, Keep NH, Solomon E. Genetic analysis of BRCA1 ubiquitin ligase activity and its relationship to breast cancer susceptibility. Hum Mol Genet 2006; 15(4): 599-606.
5. 5- Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, et al. BRCA1 physically associates with p53 and stimulates its transcriptional activity. Oncogene 1998;16(13):1713-21.
6. 6- Huyton T, Bates PA, Zhang X, Sternberg MJE, Freemont PS. The BRCA1 C-terminal domain: structure and function. Mutat Res Repair 2000; 460(3): 319-32.
7. 7- Forat-yazdi M, Neamatzadeh H, Sheikhha MH, Zare-Shehneh M, Fattahi M. BRCA1 and BRCA2 Common Mutations in Iranian Breast Cancer Patients : a Meta Analysis. Asian Pac J Cancer Prev 2015; 16(3): 1219-24. [Persian]
8. 8- Keshavarzi F, Javadi GR, Zeinali S. BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients. Fam Cancer 2012; 11(1): 57-67.
9. 9- Zoure AA, Slaoui M, Bambara HA, Sawadogo AY, Compaoré TR, Mzibri M El, et al. BRCA1 c.68_69delAG (exon2), c.181T>G (exon5), c.798_799delTT and 943ins10 (exon11) mutations in Burkina Faso 2018; 9:11-5.
10. 10- Dufloth RM, Carvalho S, Heinrich JK, Shinzato JY, dos Santos CC, Zeferino LC, et al. Analysis of BRCA1 and BRCA2 mutations in Brazilian breast cancer patients with positive family history. Sao Paulo Med J 2005; 123(4):192-7.
11. 11- Ruść A, Kamiński S. Prevalence of complex vertebral malformation carriers among Polish Holstein-Friesian bulls. J Appl Genet 2007; 48(3): 247-52.
12. 12- Wang B. BRCA1 tumor suppressor network: focusing on its tail. Cell Biosci. BioMed Central Ltd 2012; 2(1): 6.
13. 13- Chen XR, Zhang WZ, Lin XQ, Wang JW. Genetic instability of BRCA1 gene at locus D17S855 is related to clinicopathological behaviors of gastric cancer from Chinese population. World J Gastroenterol 2006; 12(26): 4246-9.
14. 14- 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.
15. 15- Blay P, Santamaría I, Pitiot AS, Luque M, Alvarado MG, Lastra A, et al. Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain). BMC Cancer 2013; 13: 243.
16. 16- Drost R, Jonkers J. Opportunities and hurdles in the treatment of BRCA1-related breast cancer. Oncogene. Oncogene 2014; 33(29): 3753-63.
17. 17- Henderson BR. The BRCA1 Breast Cancer Suppressor: Regulation of Transport, Dynamics, and Function at Multiple Subcellular Locations. Scientifica (Cairo) 2012; 2012: 796808.
18. 18- West SC. Molecular views of recombination proteins and their control. Nat Rev Mol Cell Biol 2003; 4(6): 435-45.
19. 19- Sarvar F, Nekoeian R, Saei Rad S, Gharavi MJ, Tehrani M, Taherabadi MS, et al. Evaluating the most common mutation in BRCAI and BRCA2 genes in women who had mothers with brest cancer and controls. J Maz Uni Med Sci 2016; 26(141): 137-42. [Persian]
20. 20- Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 2009; 101(2): 80-7.
21. 21- Chehade R, Pettapiece-Phillips R, Salmena L, Kotlyar M, Jurisica I, Narod SA, et al. Reduced BRCA1 transcript levels in freshly isolated blood leukocytes from BRCA1 mutation carriers is mutation specific. Breast Cancer Res 2016;18(1): 87.
22. 22- Huzarski T, Byrski T, Gronwald J, Górski B, Domagała P, Cybulski C, et al. Ten-year survival in patients with BRCA1-negative and BRCA1-positive breast cancer. J Clin Oncol 2013; 31(26): 3191-6.
23. 23- Yao L, Sun J, Zhang J, He Y, Ouyang T, Li J, et al. Breast cancer risk in Chinese women with BRCA1 or BRCA2 mutations. Breast Cancer Res Treat 2016; 156(3): 441-5.
24. 24- Casilli F, Di Rocco ZC, Gad S, Tournier I, Stoppa-Lyonnet D, Frebourg T, et al. Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments. Hum Mutat 2002; 20(3): 218-26.

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