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24.05.2022 | Epidemiology

PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina

verfasst von: Ariana Gonzalez, Franco Del Greco, Laura Vargas-Roig, Bianca Brun, Gonzalo Tabares, Alejandra Mampel, Cecilia Montes, Claudia Martin, Marcela Lopez, Norma Rossi, Luisina Bruno, Carolina Ponce, Patricia Quaglio, Alvaro Yanzi, Santiago Acevedo, Lilia Lugo, Paula Lopez Breccia, Silvia Avila, Silvina Sisterna, María Soledad Del Castillo, Martín Vazquez, Lina M. Nuñez

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2022

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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.

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Titel: PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina
verfasst von: Ariana Gonzalez
Franco Del Greco
Laura Vargas-Roig
Bianca Brun
Gonzalo Tabares
Alejandra Mampel
Cecilia Montes
Claudia Martin
Marcela Lopez
Norma Rossi
Luisina Bruno
Carolina Ponce
Patricia Quaglio
Alvaro Yanzi
Santiago Acevedo
Lilia Lugo
Paula Lopez Breccia
Silvia Avila
Silvina Sisterna
María Soledad Del Castillo
Martín Vazquez
Lina M. Nuñez
Publikationsdatum: 24.05.2022
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2022
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-022-06620-5

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PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina