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

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

Oncotarget

Albany, Nueva York: Journals Impact

Año: 2016

1949-2553

ABSTRACTBRCA1/2 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.