Ariana Gonzalez1, Franco Del Greco1, Laura Vargas-Roig2, Bianca Brun1, Gonzalo Tabares3, Alejandra Mampel4, Cecilia Montes5, Claudia Martin6, Marcela Lopez7, Norma Rossi8, Luisina Bruno9, Carolina Ponce9, Patricia Quaglio10, Alvaro Yanzi11, Santiago Acevedo12, Lilia Lugo13, Paula Lopez Breccia14, Silvia Avila15,16,17, Silvina Sisterna18, María Soledad Del Castillo5, Martín Vazquez16, Lina M Nuñez19. 1. Heritas, Rosario, Argentina. 2. IMBECU-CONICET-UNCuyo, Mendoza, Argentina. 3. CEMA Centro de Mastología Rosario, Rosario, Argentina. 4. Universidad Nacional de Cuyo - COIR, Mendoza, Argentina. 5. Instituto Modelo de Ginecología Y Obstetricia, Córdoba, Argentina. 6. Hospital Privado Universitario de Córdoba, Córdoba, Argentina. 7. CEMAFE, Santa Fe, Argentina. 8. Fundación Para el Progreso de La Medicina, Córdoba, Argentina. 9. Instituto de Oncología Alexander Fleming, Buenos Aires, Argentina. 10. Laboratorio Cigen, Rosario, Argentina. 11. Instituto San Marcos, San Juan, Argentina. 12. Hospital Británico de Buenos Aires, Buenos Aires, Argentina. 13. Clínica San Gerónimo, Santa Fe, Argentina. 14. Instituto de Ginecología de Rosario, Rosario, Argentina. 15. Facultad de Ciencias Médicas, Universidad Nacional del Comahue, Neuquén, Argentina. 16. Heritas - CONICET, Rosario, Argentina. 17. Hospital Alemán de Buenos Aires, Buenos Aires, Argentina. 18. Hospital Privado de Comunidad, Mar del Plata, Argentina. 19. Hospital Alemán de Buenos Aires, Buenos Aires, Argentina. linamnunez@gmail.com.
Abstract
PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.
PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.
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