Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice

CARDOSO FC1; CARLOS BAS; EDUARDO GONZALEZ; JOSÉ DAVALOS MICHEL; IGNACIO MC LEAN; VANESA ROMANO; GUSTAVO CORTESE; GONZALO RECONDO; MARÍA LAURA BARRIENTOS; SOLANO ANGELA; EDUARDO ABALO; ANTONIO LORUSSO; FLORENCIA PERAZZO; LINA MARÍA NUÑEZ; FRANCISCO BERNARDO SANTILLAN; ENRIQUE DIAZ CANTON; MARÍA VINIEGRA; EDUARDO BECCAR VARELA; CRISTINA MARIA NOBLIA; SILVIA ADELA AVILA; REINALDO DANIEL CHACON; ERNESTO JORGE PODESTA; MARTÍN GRECO; HECTOR DANIEL VUOTTO; OSCAR GASPAR MANDO

Oncotarget

Albany, N.Y. : Impact Journals

Lugar: Nueva York; Año: 2016

1949-2553

Abstract BRCA1/2 mutations in Latin America are scarcely documented and in serious need of knowledge about the spectrum of BRCA pathogenic variants, information which may alter clinical practice and subsequently improve patient outcome. In addition, the search for data on testing policies in different regions constitutes a fundamental strength for the present study, which analyzes BRCA1/2 gene sequences and large rearrangements in 940 probands with familial and/or personal history of breast/ovary cancer (BOC). In non-mutated DNA samples, Multiplex Ligation-dependent Probe Amplification assays (MLPA) were used for the analysis of large rearrangements. Our studies detected 179 deleterious mutations out of 940 (19.04%) probands, including 5 large rearrangements and 22 novel mutations. The recurrent mutations accounted for 15.08% of the total and only 2.87% of the probands analyzed, very different from a Hispanic panel previously described. In conclusion: a) this first comprehensive description of the spectrum in BRCA1/2 sheds light on the low frequency of recurrent mutations; b) this information is key in clinical practice to select adequate sequencing studies in our population, subsequently improve patient outcome and prevent damage associated to false normal reports resulting from the use of invalid population panels; c) panels of mutations from other populations should be cautiously validated before imported, even those of apparently similar origin, a concept to be considered beyond significance in Argentina.