Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia

Purpose: The main risk factor for familial breast cancer is the presence of mutations in BRCA1 and BRCA2 genes. The prevalence of mutations in these genes is heterogeneous and varies according to geographical origin of studied families. In Colombia mutations in these genes have been mainly studied o...

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Autores:
Cortés, Carolina
Cifuentes C, Laura
Rivera, Ana Lucia
Trochéz, David
Solarte, Melissa
Goméz, Daniela
Cifuentes, Laura
Barreto, Guillermo
Tipo de recurso:
Article of journal
Fecha de publicación:
2019
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
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OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/16082
Acceso en línea:
https://hdl.handle.net/20.500.12494/16082
Palabra clave:
Cáncer de mama
BRCA1
BRCA2
Mutaciones germinales
Cáncer Familiar
Breast cancer
BRCA1
BRCA2
Germline mutations
Familial cancer
Rights
openAccess
License
Atribución – No comercial – Sin Derivar
id COOPER2_ce52fd4054d4f051efc1344129380838
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/16082
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
title Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
spellingShingle Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
Cáncer de mama
BRCA1
BRCA2
Mutaciones germinales
Cáncer Familiar
Breast cancer
BRCA1
BRCA2
Germline mutations
Familial cancer
title_short Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
title_full Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
title_fullStr Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
title_full_unstemmed Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
title_sort Mutational Analysis of BRCA1 and BRCA2 Genes in Women With Familial Breast Cancer From Different Regions of Colombia
dc.creator.fl_str_mv Cortés, Carolina
Cifuentes C, Laura
Rivera, Ana Lucia
Trochéz, David
Solarte, Melissa
Goméz, Daniela
Cifuentes, Laura
Barreto, Guillermo
dc.contributor.author.none.fl_str_mv Cortés, Carolina
Cifuentes C, Laura
Rivera, Ana Lucia
Trochéz, David
Solarte, Melissa
Goméz, Daniela
Cifuentes, Laura
Barreto, Guillermo
dc.subject.spa.fl_str_mv Cáncer de mama
BRCA1
BRCA2
Mutaciones germinales
Cáncer Familiar
topic Cáncer de mama
BRCA1
BRCA2
Mutaciones germinales
Cáncer Familiar
Breast cancer
BRCA1
BRCA2
Germline mutations
Familial cancer
dc.subject.other.spa.fl_str_mv Breast cancer
BRCA1
BRCA2
Germline mutations
Familial cancer
description Purpose: The main risk factor for familial breast cancer is the presence of mutations in BRCA1 and BRCA2 genes. The prevalence of mutations in these genes is heterogeneous and varies according to geographical origin of studied families. In Colombia mutations in these genes have been mainly studied on patients from Andean region. Bogotá and Medellin presented its own battery of mutations. This study aims to identify mutations in BRCA1-2 genes in women with familial breast cancer from different regions of Colombia. Methods: One hundred four families with a history of breast cancer were sampled in different regions of Colombia, and the BRCA1 gene and exon 11 of the BRCA2 gene were sequenced. To predict the possible effects of sequence alterations found in protein function, different bioinformatics tools were used. Results: A total of 33 variants were found; 18 in BRCA1 and 15 in BRCA2, of which 15 are unique variants of Colombia. In silico analysis established that alterations p.Thr790Ala, p.Arg959Lys and p.Glu1345Lys in the BRCA1 gene and variants p.Leu771Phe, p.Asn818Lys, p.Val859Ser*22 and p.Lys1032Ile in the BRCA2 gene are considered likely pathogenic. Both the mutations as the variants of unknown clinical significance, in their great majority, presented a specific region distribution and they were different from those reported in previous studies. Conclusions: In this study we report the BRCA1 and BRCA2 spectrum of mutations and their distribution by regions in Colombia. Our results may help to design a diagnostic test including recurrent mutations for screening high risk to breast cancer families in Colombia.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019-07-15
dc.date.accessioned.none.fl_str_mv 2020-01-20T13:44:05Z
dc.date.available.none.fl_str_mv 2020-01-20T13:44:05Z
dc.type.none.fl_str_mv Artículo
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
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dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.issn.spa.fl_str_mv 1897-4287
dc.identifier.uri.spa.fl_str_mv 10.1186/s13053-019-0120-x
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/16082
dc.identifier.bibliographicCitation.spa.fl_str_mv Cortés, C., Rivera, A. L., Trochez, D., Solarte, M., Gómez, D., Cifuentes, L., & Barreto, G. (2019). Mutational analysis of BRCA1 and BRCA2 genes in women with familial breast cancer from different regions of Colombia. Hereditary cancer in clinical practice, 17(1), 20. Recuperado de: https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-019-0120-x
identifier_str_mv 1897-4287
10.1186/s13053-019-0120-x
Cortés, C., Rivera, A. L., Trochez, D., Solarte, M., Gómez, D., Cifuentes, L., & Barreto, G. (2019). Mutational analysis of BRCA1 and BRCA2 genes in women with familial breast cancer from different regions of Colombia. Hereditary cancer in clinical practice, 17(1), 20. Recuperado de: https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-019-0120-x
url https://hdl.handle.net/20.500.12494/16082
dc.relation.isversionof.spa.fl_str_mv https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-019-0120-x
dc.relation.ispartofjournal.spa.fl_str_mv Hereditary Cancer in Clinical Practice
dc.relation.references.spa.fl_str_mv 1. DeSantis CE, Ma J, Goding A, Newman LA, Jemal A. Breast Cancer Statistics,2017, Racial Disparity in Mortality by State. CA Cancer J Clin. 2017;67(6):439-448.
2. Instituto Nacional de Cancerología ESE. Anuario estadístico. 2018. http://www.cancer.gov.co/files/libros/archivos/ANUARIO. Accessed 23 June 2018.
3. Oldenburg RA, Meijers-Heijboer H, Cornlisse CJ, Devilee P. Genetic susceptibility for breast cancer: how many more genes to be found? Crit Rev Oncol Hematol. 2007;63(2):125-49.
4. Schwab FD, Burki N, Huang DJ, Heinzelmann-schwarz V, Schmid SM, Vetter M, Schotzau A, Guth U. Impact of breast cancer family history on tumor detection and tumor size in women newly-diagnosed with invasive breast cancer. Fam Cancer. 2014;13(1):99-107.
5. Oosterwijk JC, De Vries J, Mourits MJ, De Bock GH. Genetic testing and familial implications in breast-ovarian cancer families. Maturitas. 2014;78(4):252-7.
6. Pettigrew CA, French JD, Saunus JM, Edwards SL, Sauer AV, Smart CE, Lundstrom T, Wiesner C, Spurdle AB, Rothangel JA, Brown MA. Identification and functional analysis of novel BRCA1 transcripts including mouse Brca1-Iris and human pseudo-BRCA1. Breast Cancer Res Treat. 2010;119(1):239-47
7. Clark S, Rodriguez A, Snyder R, Hankins G, Boehning D. Structure-Function of the tumor supressor BRCA1. Comput Struct Biotechnol J. 2012;1:e201204005.
8. Barnes DR, Antoniou AC. Unravelling modifiers of breast and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: update on genetic modifiers. J Intern Med. 2012;271(4):331–43.
9. Torres D, Rashid MU, Gil F, Umana A, Ramelli G, Robledo JF, Tawil M, Torregrosa L, Briceno I, Hamann U. High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Res. Treat. 2007;103(2):225–32
10. Torres D, Umaña A, Robledo JF, Caicedo JJ, Quintero E, Orozco A, Torregrosa L, Tawil M, Hamman U, Briceño I. Estudio de factores genéticos para cáncer de mama en Colombia. Universitas Médica. 2009;50 (3):297–301.
11. Londoño-Hernández JE, Llacuachagui M, Vasquez-Palacio G, Figueroa JD, Madrid J, Lema M, Royer R, Song L, Larson G, Weitzel J, Narod S. Prevalence of BRCA1 and BRCA2 mutations in unselected Breast cancer patients from Medellin Colombia. Hered Cancer Clin Pract. 2014;12(1):11
12. Cock‑Rada AM, Ossa CA, Garcia HI, Gomez LR. A multi-gene panel study in hereditary breast and ovarian cancer in Colombia. Fam Cancer. 2018;17(1):23-30.
13. Briceño-Balcázar I, Gomez-Gutierrez A, Diaz-Dussan NA, Noguera-Santamaría MC, Diaz-Rincón D, Casas-Gómez MC. Mutational spectrum in breast cancer associated BRCA1 and BRCA2 genes in Colombia. Colomb Med. 2017;48(2):58-63.
14. Torres D, Bermejo JL, Rashid MU, Briceño I, Gil F, Beltran A, Ariza V, Hamann U. Prevalence and Penetrance of BRCA1 and BRCA2 Germline Mutations in Colombian Breast Cancer Patients. Sci Rep. 2017;7(1):4713
15. Stoppa-Lyonnet D, Laurent-Puig P, Essioux L, Pages S, Ithier G. Ligot L, Fourquet A, Salmon RJ, Clough KB, Pouillart P, Bonaiti-Pellie C, Thomas G. BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Am J Hum Genet. 1997;60(5):1021-1030
16. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215
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18. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding nonsynonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073-81
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22. Mi H, Muruganujan A, Thomas PD. Panther in 2013: modeling the evolution of gene function and other gene attributes in the context of phylogenetic trees. Nucleic Acids Res. 2013;41(Database issue):D377-86.
23. Tavtigian SV, Deffenbaugh AM, Yin L, Judkins T, Scholl T, Samollow PB, De Silva D, Zharkikh A, Thomas A. Comprehensive Statistical Study of 452 Brca1 missense substitutions with classification of eight recurrent substitutions as neutral. J Med Genet. 2006;43(4):295-305
24. Capriotti E, Calabrese R, Fariselli P, Martelli PL, Altman RB, Casadio R. WS-SNP&GO: a web server for predicting the deleterious effect of human protein variants using functional annotation. BMC Genomics. 2013;14(3):S6
25. Alamut Visual Interactive Biosoftware Rouen France 2017. http://wwwinteractivebiosoftwarecom/alamut-visual. Accessed 15 November 2017.
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27. Joslyn SA, West MM. Racial differences in breast carcinoma survival. Cancer. 2000;88(1):114-23.
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29. Donald JE, Kulp DW, Degrado WF. Salt bridges: geometrically specific, designable interactions Proteins. Proteins. 2011;79(3):898-915.
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36. Ashton-Prolla P, Vargas FR. Prevalence and impact of founder mutations in hereditary breast cancer in Latin America. Genet Mol Biol. 2014;37(1):234-40.
37. Díez O, Osorio A, Dúran M, Martinez-Ferrandis JI, De la Hoya M, Salazar R, Vega A, Campos B, Rodríguez-López R, Velasco E, Chaves J, Díaz-Rubio E, Jesús-Cruz J, Torres M, Esteban E, Cervantes A, Alonso C, San Román JM, González-Sarmiento R, Miner C, Carracedo A, Eugenia-Armengod M, Caldés T, Benítez J, Baiget M. Analysis of BRCA1 and BRCA2 genes in Spanish Breast/Ovarian cancer patients: A high proportion of mutations unique to Spain and evidence of founder effect. Hum Mutat. 2003;22(4):301-12
38. Buleje J, Guevara-Fujita M, Acosta O, Huaman F, Danos P, Murillo A, Pinto JA, Araujo JM, Aguilar A, Ponce J, Vigil C, Castaneda C, Calderon G, Gomez HL, Fujita R. Mutational analysis of BRCA1 and BRCA2 genes in Peruvian families with hereditary breast and ovarian cancer. Mol Genet Genomic Med. 2017;5(5):481-494.
39. Lara K, Consigliere N, Pérez J, Porco A. BRCA1 and BRCA2 mutations in Breast cancer patients from Venezuela. Biol Res. 2012;45(2):117-30.
40. Solano AR, Aceto GM, Delettieres D, Veschi S, Neuman MI, Alonso E, Chialina S, Chacón RD, Renato MC, Podestá EJ. BRCA1 and BRCA2 analysis of Argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin. SpringerPlus. 2012;1:20.
41. Bella S, Llugdar J, Biagi-Bistoni M, Pelliccioni P, Lerda D, Labrador J, Fernandez-Cruz G, Martins C, Illescas E. Frequency of Mutations in Brca1 and Brca2 Genes in Women with Breast Cancer in Córdoba, Argentina. AJCS. 2015;1(1):11-16.
42. Palmero EI, Alemar B, Schuller-Faccini L, Hainaut P, Moreira-Filho CA, Petroni-Ewald I, Koehler-dos Santos P, Izetti-Ribeiro PL, De Oliveira-Netto CB, Le Calvez-Kelm F, Tavtigian S. Screening for germline BRCA1, BRCA2, TP53 and CHEK2 mutations in families at risk for hereditary breast cancer identified in a population-based study from Southern Brazil. Genet Mol Biol. 2016;39(2):210-222.
43. Porto-Cotrim D, Goncalves-Ribeiro AR, Paixao D, Cordeiro de Queiroz D, Jbili R, Carvalho-Pandolfi N, Cezana C, De Cassia-Mauro C, Mantoan H, Bovolim G, De Brot L, Tardin-Torrezan G, Carraro DM, Baiocchi G, Da Cruz-Formiga MN. Prevalence of BRCA1 and BRCA2 pathogenic and likely pathogenic variants in non-selected ovarian carcinoma patients in Brazil. BMC Cancer. 2019;19:4.
44. Vaca-Paniagua F, Alvarez-Gomez RM, Fragoso-Ontiveros V, Vidal-Millan S, Herrera LA, Cantú D, Bargallo-Rocha E, Mohar A, López-Camarillo C, Pérez-Plasencia C. Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer. PLoS One. 2012;7(5):e37432.
45. Jara L, Ampuero S, Santibáñez E, Seccia L, Rodríguez J, Bustamante M, Martínez V, Catenaccio A, Lay-Son G, Blanco R, Reyes JM. BRCA1 and BRCA2 mutations in a South American population. Cancer Genet Cytogenet. 2006;166(1):36-45.
46. Gonzalez-Hormazabal P, Gutierrez-Enriquez S, Gaete D, Reyes JM, Peralta O, Waugh E, Jara L. Spectrum of BRCA1/2 point mutations and genomic rearrangements in high-risk breast/ovarian cancer Chilean families. Breast Cancer Res Treat. 2011;126(3):705-16.
47. Rodríguez AO, Llacuachaqui M, Pardo GG, Royer R, Larson G, Weitzel JN, Narod SA. BRCA1 and BRCA2 mutations among ovarian cancer patients from Colombia. Gynecol Oncol. 2012;124(2):236–43.
48. Rojas W, Parra MV, Campo O, Caro MA, Lopera JG, Arias W, Duque C, Naranjo A, García J, Vergara C, Lopera J, Hernandez E, Valencia A, Caicedo Y, Cuartas M, Gutiérrez J, López S, Ruiz-Linares A, Bedoya G. Genetic makeup and structure of Colombian populations by means of uniparental and biparental DNA markers. Am J Phys Anthropol. 2010;143(1):13-20.
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spelling Cortés, CarolinaCifuentes C, LauraRivera, Ana LuciaTrochéz, DavidSolarte, MelissaGoméz, DanielaCifuentes, LauraBarreto, Guillermo172020-01-20T13:44:05Z2020-01-20T13:44:05Z2019-07-151897-428710.1186/s13053-019-0120-xhttps://hdl.handle.net/20.500.12494/16082Cortés, C., Rivera, A. L., Trochez, D., Solarte, M., Gómez, D., Cifuentes, L., & Barreto, G. (2019). Mutational analysis of BRCA1 and BRCA2 genes in women with familial breast cancer from different regions of Colombia. Hereditary cancer in clinical practice, 17(1), 20. Recuperado de: https://hccpjournal.biomedcentral.com/articles/10.1186/s13053-019-0120-xPurpose: The main risk factor for familial breast cancer is the presence of mutations in BRCA1 and BRCA2 genes. The prevalence of mutations in these genes is heterogeneous and varies according to geographical origin of studied families. In Colombia mutations in these genes have been mainly studied on patients from Andean region. Bogotá and Medellin presented its own battery of mutations. This study aims to identify mutations in BRCA1-2 genes in women with familial breast cancer from different regions of Colombia. Methods: One hundred four families with a history of breast cancer were sampled in different regions of Colombia, and the BRCA1 gene and exon 11 of the BRCA2 gene were sequenced. To predict the possible effects of sequence alterations found in protein function, different bioinformatics tools were used. Results: A total of 33 variants were found; 18 in BRCA1 and 15 in BRCA2, of which 15 are unique variants of Colombia. In silico analysis established that alterations p.Thr790Ala, p.Arg959Lys and p.Glu1345Lys in the BRCA1 gene and variants p.Leu771Phe, p.Asn818Lys, p.Val859Ser*22 and p.Lys1032Ile in the BRCA2 gene are considered likely pathogenic. Both the mutations as the variants of unknown clinical significance, in their great majority, presented a specific region distribution and they were different from those reported in previous studies. Conclusions: In this study we report the BRCA1 and BRCA2 spectrum of mutations and their distribution by regions in Colombia. Our results may help to design a diagnostic test including recurrent mutations for screening high risk to breast cancer families in Colombia.https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=00002608190000-0001-7013-1952https://scienti.minciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000002911laura.cifuentesc@campusucc.edu.cohttps://scholar.google.com/citations?user=MKqJTTAAAAAJ&hl=en10Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Odontología, PastoOdontologíaPastohttps://hccpjournal.biomedcentral.com/articles/10.1186/s13053-019-0120-xHereditary Cancer in Clinical Practice1. DeSantis CE, Ma J, Goding A, Newman LA, Jemal A. Breast Cancer Statistics,2017, Racial Disparity in Mortality by State. CA Cancer J Clin. 2017;67(6):439-448.2. Instituto Nacional de Cancerología ESE. Anuario estadístico. 2018. http://www.cancer.gov.co/files/libros/archivos/ANUARIO. Accessed 23 June 2018.3. Oldenburg RA, Meijers-Heijboer H, Cornlisse CJ, Devilee P. Genetic susceptibility for breast cancer: how many more genes to be found? Crit Rev Oncol Hematol. 2007;63(2):125-49.4. Schwab FD, Burki N, Huang DJ, Heinzelmann-schwarz V, Schmid SM, Vetter M, Schotzau A, Guth U. Impact of breast cancer family history on tumor detection and tumor size in women newly-diagnosed with invasive breast cancer. Fam Cancer. 2014;13(1):99-107.5. Oosterwijk JC, De Vries J, Mourits MJ, De Bock GH. Genetic testing and familial implications in breast-ovarian cancer families. Maturitas. 2014;78(4):252-7.6. Pettigrew CA, French JD, Saunus JM, Edwards SL, Sauer AV, Smart CE, Lundstrom T, Wiesner C, Spurdle AB, Rothangel JA, Brown MA. Identification and functional analysis of novel BRCA1 transcripts including mouse Brca1-Iris and human pseudo-BRCA1. Breast Cancer Res Treat. 2010;119(1):239-477. Clark S, Rodriguez A, Snyder R, Hankins G, Boehning D. Structure-Function of the tumor supressor BRCA1. Comput Struct Biotechnol J. 2012;1:e201204005.8. Barnes DR, Antoniou AC. Unravelling modifiers of breast and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: update on genetic modifiers. J Intern Med. 2012;271(4):331–43.9. Torres D, Rashid MU, Gil F, Umana A, Ramelli G, Robledo JF, Tawil M, Torregrosa L, Briceno I, Hamann U. High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Res. Treat. 2007;103(2):225–3210. Torres D, Umaña A, Robledo JF, Caicedo JJ, Quintero E, Orozco A, Torregrosa L, Tawil M, Hamman U, Briceño I. Estudio de factores genéticos para cáncer de mama en Colombia. Universitas Médica. 2009;50 (3):297–301.11. Londoño-Hernández JE, Llacuachagui M, Vasquez-Palacio G, Figueroa JD, Madrid J, Lema M, Royer R, Song L, Larson G, Weitzel J, Narod S. Prevalence of BRCA1 and BRCA2 mutations in unselected Breast cancer patients from Medellin Colombia. Hered Cancer Clin Pract. 2014;12(1):1112. Cock‑Rada AM, Ossa CA, Garcia HI, Gomez LR. A multi-gene panel study in hereditary breast and ovarian cancer in Colombia. Fam Cancer. 2018;17(1):23-30.13. Briceño-Balcázar I, Gomez-Gutierrez A, Diaz-Dussan NA, Noguera-Santamaría MC, Diaz-Rincón D, Casas-Gómez MC. Mutational spectrum in breast cancer associated BRCA1 and BRCA2 genes in Colombia. Colomb Med. 2017;48(2):58-63.14. Torres D, Bermejo JL, Rashid MU, Briceño I, Gil F, Beltran A, Ariza V, Hamann U. Prevalence and Penetrance of BRCA1 and BRCA2 Germline Mutations in Colombian Breast Cancer Patients. Sci Rep. 2017;7(1):471315. 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Rojas W, Parra MV, Campo O, Caro MA, Lopera JG, Arias W, Duque C, Naranjo A, García J, Vergara C, Lopera J, Hernandez E, Valencia A, Caicedo Y, Cuartas M, Gutiérrez J, López S, Ruiz-Linares A, Bedoya G. Genetic makeup and structure of Colombian populations by means of uniparental and biparental DNA markers. 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