Analysis of BRCA1and BRCA2 large genomic rearrangements in Sri Lankan familial breast cancer patients and at risk individuals

BMC Research Notes

Preethika Angunawela³  Indrani Amarasinghe²  Eric Hamilton Karunanayake¹  Kamani Hemamala Tennekoon¹  Sumadee De Silva¹ 

[1] Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka;National Cancer Institute, Colombo, Sri Lanka;Department of Pathology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

关键词: Breast cancer;    Large genomic rearrangements;    BRCA2;    BRCA1;   

Others  :  1132535
DOI  :  10.1186/1756-0500-7-344

 received in 2013-12-21, accepted in 2014-05-29,  发布年份 2014

【 摘 要 】

Background

Majority of mutations found to date in the BRCA1/BRCA2 genes in breast and/or ovarian cancer families are point mutations or small insertions and deletions scattered over the coding sequence and splice junctions. Such mutations and sequence variants of BRCA1 and BRCA2 genes were previously identified in a group of Sri Lankan breast cancer patients. Large genomic rearrangements have been characterized in BRCA1 and BRCA2 genes in several populations but these have not been characterized in Sri Lankan breast cancer patients.

Findings

A cohort of familial breast cancer patients (N = 57), at risk individuals (N = 25) and healthy controls (N = 23) were analyzed using multiplex ligation-dependent probe amplification method to detect BRCA1 and BRCA2 large genomic rearrangements. One familial breast cancer patient showed an ambiguous deletion in exon 6 of BRCA1 gene. Full sequencing of the ambiguous region was used to confirm MLPA results. Ambiguous deletion detected by MLPA was found to be a false positive result confirming that BRCA1 large genomic rearrangements were absent in the subjects studied. No BRCA2 rearrangement was also identified in the cohort.

Conclusion

Thus this study demonstrates that BRCA1 and BRCA2 large genomic rearrangements are unlikely to make a significant contribution to aetiology of breast cancer in Sri Lanka.

【 授权许可】

   
2014 De Silva et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Martin AM, Blackwood MA, Antin-Ozerkis D, Shih HA, Calzone K, Colligon TA, Seal S, Collins N, Stratton MR, Weber BL, Nathanson KL: Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast cancer risk evaluation clinic. J Clin Oncol 2001, 19:2247-2253.
• [2]Peto J: Cancer epidemiology in the last century and the next decade. Nature 2001, 411:390-395.
• [3]Fackenthal JD, Olopade OI: Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer 2007, 7:937-948.
• [4]Cancer Incidence Data Sri Lanka Year 2001–2005: Cancer Registry National Cancer Control Programme. Colombo 5; 2009.
• [5]De Silva W, Karunanayake EH, Tennekoon KH, Allen M, Amarasinghe I, Angunawala P, Ziard MH: Novel sequence variants and a high frequency of recurrent polymorphisms in BRCA1 gene in Sri Lankan breast cancer patients and at risk individuals. BMC Cancer 2008, 8:214. BioMed Central Full Text
• [6]De Silva S, Tennekoon KH, Karunanayake EH, De Silva W, Amarasinghe I, Angunawela P: Novel sequence variants and common recurrent polymorphisms of BRCA2 in Sri Lankan breast cancer patients and a family with BRCA1 mutations. Exp Ther Med 2011, 2:1163-1170.
• [7]Mazoyer S: Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat 2005, 25:415-422.
• [8]Seong MW, Cho SI, Noh DY, Han W, Kim SW, Park CM, Park HW, Kim SY, Kim JY, Park SS: Low contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer in the Korean population. Fam Cancer 2009, 8:505-508.
• [9]Lim YK, Lau PT, Ali AB, Lee SC, Wong JE, Putti TC, Sng JH: Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer. Clin Genet 2007, 71:331-342.
• [10]Kang P, Mariapun S, Phuah SY, Lim LS, Liu J, Yoon SY, Thong MK, Mohd Taib NA, Yip CH, Teo SH: Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families. Breast Cancer Res Treat 2010, 124:579-584.
• [11]Kwong A, Ng EK, Law FB, Wong HN, Wa A, Wong CL, Kurian AW, West DW, Ford JM, Ma ES: Novel BRCA1 and BRCA2 genomic rearrangements in Southern Chinese breast/ovarian cancer patients. Breast Cancer Res Treat 2012, 136:931-933.
• [12]de la Hoya M, Gutiérrez-Enríquez S, Velasco E, Osorio A, Sanchez de Abajo A, Vega A, Salazar R, Esteban E, Llort G, Gonzalez-Sarmiento R, Carracedo A, Benítez J, Miner C, Díez O, Díaz-Rubio E, Caldes T: Genomic rearrangements at the BRCA1 locus in Spanish families with breast/ovarian cancer. Clin Chem 2006, 52:1480-1485.
• [13]Torres D, Rashid MU, Seidel-Renkert A, Weitzel JN, Briceno I, Hamann U, Colombian Breast Cancer Study Group (COLBCS): Absence of the BRCA1 del (exons 9–12) mutation in breast/ovarian cancer families outside of Mexican Hispanics. Breast Cancer Res Treat 2009, 117:679-681.
• [14]Pylkas K, Erkko H, Nikkila J, Solyom S, Winqvist R: Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families. BMC Cancer 2008, 8:146. BioMed Central Full Text
• [15]Deininger PL, Batzer MA: Alu repeats and human disease. Mol Genet Metab 1999, 67:183-193.
• [16]Smith TM, Lee MK, Szabo CI, Jerome N, McEuen M, Taylor M, Hood L, King MC: Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCAI. Genome Res 1996, 6:1029-1049.
• [17]Puget N, Gad S, Perrin-Vidoz L, Sinilnikova OM, Stoppa-Lyonnet D, Lenoir GM, Mazoyer S: Distinct BRCA1 rearrangements involving the BRCA1 pseudogene suggest the existence of a recombination hot spot. Am J Hum Genet 2002, 70:858-865.
• [18]Montagna M, Santacatterina M, Torri A, Menin C, Zullato D, Chieco-Bianchi L, D'Andrea E: Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast/ovarian cancer families. Oncogene 1999, 18:4160-4165.
• [19]Stadler ZK, Saloustros E, Hansen NA, Schluger AE, Kauff ND, Offit K, Robson ME: Absence of genomic BRCA1 and BRCA2 rearrangements in Ashkenazi breast and ovarian cancer families. Breast Cancer Res Treat 2010, 123:581-585.
• [20]Sluiter MD, van Rensburg EJ: Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation. Breast Cancer Res Treat 2011, 125:325-349.
• [21]Mahon SM: Large genomic rearrangements in BRCA1 and BRCA2. Implications for patient care. Oncol Nurs Forum 2013, 40:220-222.
• [22]Thomassen M, Gerdes AM, Cruger D, Jensen PK, Kruse TA: Low frequency of large genomic rearrangements of BRCA1 and BRCA2 in Western Denmark. Cancer Genet Cytogenet 2006, 168:168-171.
• [23]Gad S, Caux-Moncoutier V, Pages-Berhouet S, Gauthier-Villars M, Coupier I, Pujol P, Frénay M, Gilbert B, Maugard C, Bignon YJ, Chevrier A, Rossi A, Fricker JP, Nguyen TD, Demange L, Aurias A, Bensimon A, Stoppa-Lyonnet D: Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families. Oncogene 2002, 21:6841-6847.
• [24]Miller SA, Dykes DD, Poleskey HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988, 16:12-15.