Hereditary breast and ovary cancer in Uruguay
screening results for mutations in susceptibility genes by new generation sequencing
Abstract
Introduction: breast cancer is women’s first cause of death in Uruguay. According to estimations, around 7% of cases result from germinal mutations by deoxyribonucleic acid. The cost of genetic sequencing has dramatically dropped thanks to the arrival of next-generation sequencing (NGS). This technological change opened a new era in the study of hereditary cancer in our country.
Objective: to communicate the results of using NGS technology and multigenic panels in Uruguayan families with high risk of hereditary breast cancer.
Method: 135 high risk families referred by the genetic counselling consultation that is provided at the Uruguayan Collaborative Group (Hereditary Oncological Conditions Research) were sequenced. When the family history clearly suggested hereditary breast and ovary cancer was a possibility, exclusive NGS sequencing was done for BRCA1 and BRCA2 genes; when the family pattern was not clear to this respect, multigenic panels were used.
Results: exclusive NGS sequencing for BRCA1 and BRCA2 genes was done in 62 families, and multigenic panels were used in 73 families. 29 pathogenic mutations were identified (21 in BRCA genes and 8 in other genes). Two of them were new to the disease and three could be considered recurrent in the Uruguayan population.
Conclusions: this study is the first one in Uruguay to report the results of this new technology in hereditary breast cancer. The finding of 29 pathogenic mutations contributes to outlining the mutational profile of our country.
References
(1) Uruguay. Comisión Honoraria de Lucha Contra el Cáncer. V Atlas de mortalidad por cáncer en el Uruguay: período 2009-2013. Montevideo: CHLCC, 2015. Disponible en: http://www.comisioncancer.org.uy/categoria_53_1.html (Consulta: 14 abril 2016).
(2) Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer 1996; 77(11):2318-24.
(3) Meldrum C, Doyle MA, Tothill RW. Next-generation sequencing for cáncer diagnostics: a practical perspective. Clin Biochem Rev 2011; 32(4):177-95.
(4) Delgado L, Fernández G, Grotiuz G, Cataldi S, González A, Lluveras N, et al. BRCA1 and BRCA2 germline mutations in Uruguayan breast and breast-ovarian cancer families: identification of novel mutations and unclassified variants. Breast Cancer Res Treat 2011; 128(1):211-8.
(5) United States. National Comprehensive Cancer Network. NCCN guidelines (r) insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2016. Washington, DC: NCCN, 2016. Disponible en: https://www.nccn.org/ (Consulta: 23 marzo 2016).
(6) Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17(5):405-24.
(7) Judkins T, Leclair B, Bowles K, Gutin N, Trost J, McCulloch J, et al. Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 and BRCA2 genes to assess hereditary cancer risk. BMC Cancer 2015; 15:215.
(8) Metcalfe KA, Finch A, Poll A, Horsman D, Kim-Sing C, Scott J, et al. Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation. Br J Cancer 2009; 100(2):421-5.
(9) Petrucelli N, Daly MB, Feldman GL. BRCA1 and BRCA2 hereditary breast and ovarian cancer. (Updated 2013 Sep 26). En: Pagon RA, Adam MP, Ardinger HH, eds. GeneReviews(r). Seattle (WA): University of Washington, 1993.
(10) Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 1999; 91(11):943-9.
(11) Bonilla C, Bertoni B, Hidalgo PC, Artagaveytia N, Ackermann E, Barreto I, et al. Breast cancer risk and genetic ancestry: a case-control study in Uruguay. BMC Womens Health 2015; 15:11.
(12) Solano AR, Cardoso FC, Romano V, Perazzo F, Bas C, Recondo G, et al. Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice. Oncotarget 2016 Jul 24. (Epub ahead of print).
(13) Villarreal-Garza C, Álvarez-Gómez RM, Pérez-Plasencia C, Herrera LA, Herzog J, Castillo D, et al. Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico. Cancer 2015; 121(3):372-8.
(14) Ossa CA, Torres D. Founder and Recurrent Mutations in BRCA1 and BRCA2 genes in Latin American countries: state of the art and literature review. Oncologist 2016; 21(7): 832-9.
(15) Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, et al. Clinical Actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol 2015; 1(7):943-51.
(16) Kapoor NS, Curcio LD, Blakemore CA, Bremner AK, McFarland RE, West JG, et al. Multigene panel testing detects equal rates of pathogenic BRCA1/2 mutations and has a higher diagnostic yield compared to limited BRCA1/2 Analysis Alone in Patients at Risk for Hereditary Breast cancer. Ann Surg Oncol 2015; 22(10):3282-8.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
