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. 2022 Jul;194(2):403-412.
doi: 10.1007/s10549-022-06620-5. Epub 2022 May 24.

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

Ariana Gonzalez  1 , Franco Del Greco  1 , Laura Vargas-Roig  2 , Bianca Brun  1 , Gonzalo Tabares  3 , Alejandra Mampel  4 , Cecilia Montes  5 , Claudia Martin  6 , Marcela Lopez  7 , Norma Rossi  8 , Luisina Bruno  9 , Carolina Ponce  9 , Patricia Quaglio  10 , Alvaro Yanzi  11 , Santiago Acevedo  12 , Lilia Lugo  13 , Paula Lopez Breccia  14 , Silvia Avila  15   16   17 , Silvina Sisterna  18 , María Soledad Del Castillo  5 , Martín Vazquez  16 , Lina M Nuñez  19
Affiliations

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

Ariana Gonzalez et al. Breast Cancer Res Treat. 2022 Jul.

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.

Keywords: Argentina; Breast-ovarian cancer; Germline mutations; Multi-gene panel; PALB2; Recurrent mutation.

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