Buenos Aires
Breast Cancer
Symposium

BA-BCS 2024

September 3 – 6, 2024

IFIBYNE Auditorium, FCEN-UBA

Poster No. 29

GENOMIC PROFILE OF GENETIC VARIANTS ASSOCIATED WITH HEREDITARY BREAST/OVARIAN CANCER: EXPERIENCE FROM THE ANALYSIS OF MULTIGENE PANEL TESTING IN ARGENTINA

Mayra Lis Sottile1,2, Analia Lourdes Redondo1,2, Laura Constanza Gómez1, Cecilia Montes3, Alejandra Mampel4,2, Laura Maria Vargas-Roig1,2

1.IMBECU, CCT Mendoza, CONICET, UNCuyo, Argentina 2.Facultad de Ciencias Médicas, UNCuyo, Mendoza, Argentina 3.Instituto Modelo de Ginecología & Obstetricia, Córdoba, Argentina 4. Centro Oncológico de Integración Regional (COIR), Mendoza, Argentina..

Presenting Autor:
Redondo, Analia Lourdes

IMBECU CCT Mendoza

Breast cancer (BC) is a disease with high incidence in Argentina and the leading cause of cancer death in women in our country. Hereditary BC and ovarian cancer (HBOC) are mainly caused by deleterious germline mutations in BRCA1 or BRCA2 genes. However, a number of these cancers are due to germline mutations in other susceptibility genes with low frequency or reduced penetrance. We aimed to characterize the frequency of pathogenic (P) and likely pathogenic (LP) variants in HBOC susceptibility genes in the Argentine population. 354 women from Mendoza and Cordoba with early-onset BC/OC or a family history of cancer were included. Patients were tested using NGS panel containing at least 14 high- and moderate-penetrance HBOC genes. P and LP variants were identified in 17.2% (61/354) of cases. Fifty-one of these carriers presented a diagnosis of BC (3 with bilateral BC), 5 of OC, and 5 were healthy women. The mean age of cancer diagnosis was 41.5 years. Thirty (8.5%) patients carry germline P/LP variants in BRCA1/2 and 31 (8.7%) in other HBOC susceptibility genes. A total of 66 P/LP variants were detected: 30/66 (45.4%) in BRCA1/2, 10 in PALB2 (15.2%), 5 in CHEK2 (7.6%), 3 in TP53 (4.5%), 3 in ATM (4.5%), 2 (3%) in RAD51C, MLH1, MUTYH, MITF and PMS2, and 5 in other less frequent genes. Four (0.85%) patients were double heterozygote carriers of germline P/LP variants. The co-occurrence of P/LP variants was identified in the following genes: BRCA2+BARD1, TP53+CDKN2A, MLH1+MITF and B RCA2+CHEK2. In addition, a novel LP variant was detected in BRCA2: c.1744del (p.Thr582LeufsTer2), a frameshift mutation that introduces a premature stop codon in the protein. Our findings would indicate that multigene panel testing gives more accurate information on cancer risk and thus would allow the implementation of more appropriate surveillance strategies in germline P/LP variants carriers.