Maria Fonfria1, Inmaculada de Juan Jiménez2, Isabel Tena1, Isabel Chirivella3, Paula Richart-Aznar4, Angel Segura4, Ana Beatriz Sánchez-Heras5, Eduardo Martinez-Dueñas1. 1. Cancer Genetic Counseling Unit, Medical Oncology Department, Castellon Provincial Hospital, 12002 Castellon, Spain. 2. Molecular Biology Unit, Service of Clinical Analysis, La Fe University Hospital, 46026 Valencia, Spain. 3. Medical Oncology Department, INCLIVA Biomedical Research Institute, University of Valencia, 46001 Valencia, Spain. 4. Cancer Genetic Counseling Unit, Medical Oncology Department, La Fe University Hospital, 46026 Valencia, Spain. 5. Cancer Genetic Counseling Unit, Medical Oncology Department, Elche University Hospital, 03203 Elche, Spain.
Abstract
(1) Background: Over the last decade, genetic counseling clinics have moved from single-gene sequencing to multigene panel sequencing. Multiple genes related to a moderate risk of breast cancer (BC) have emerged, although many questions remain regarding the risks and clinical features associated with these genes. (2) Methods: Ninety-six BC index cases (ICs) with high-risk features for hereditary breast and ovarian cancer (HBOC) and with a previous uninformative result for BRCA1/2 were tested with a panel of 41 genes associated with BC risk. The frequency of pathogenic variants (PVs) was related to the clinical characteristics of BC. (3) Results: We detected a PV rate of 13.5% (excluding two cases each of BRCA1 and MUTYH). Among the 95 assessed cases, 17 PVs were identified in 16 ICs, as follows: BRCA1 (n = 2), CHEK2 (n = 3), ATM (n = 5), MUTYH (n = 2), TP53 (n = 2), BRIP1 (n = 1), CASP8 (n = 1), and MSH2 (n = 1). We also identified a novel loss-of-function variant in CASP8, a candidate gene for increased BC risk. There was no evidence that the clinical characteristics of BC might be related to a higher chance of identifying a PV. (4) Conclusions: In our cohort, which was enriched with families with a high number of BC cases, a high proportion of mutations in ATM and CHEK2 were identified. The clinical characteristics of BC associated with moderate-risk genes were different from those related to BRCA1/2 genes.
(1) Background: Over the last decade, genetic counseling clinics have moved from single-gene sequencing to multigene panel sequencing. Multiple genes related to a moderate risk of breast cancer (BC) have emerged, although many questions remain regarding the risks and clinical features associated with these genes. (2) Methods: Ninety-six BC index cases (ICs) with high-risk features for hereditary breast and ovarian cancer (HBOC) and with a previous uninformative result for BRCA1/2 were tested with a panel of 41 genes associated with BC risk. The frequency of pathogenic variants (PVs) was related to the clinical characteristics of BC. (3) Results: We detected a PV rate of 13.5% (excluding two cases each of BRCA1 and MUTYH). Among the 95 assessed cases, 17 PVs were identified in 16 ICs, as follows: BRCA1 (n = 2), CHEK2 (n = 3), ATM (n = 5), MUTYH (n = 2), TP53 (n = 2), BRIP1 (n = 1), CASP8 (n = 1), and MSH2 (n = 1). We also identified a novel loss-of-function variant in CASP8, a candidate gene for increased BC risk. There was no evidence that the clinical characteristics of BC might be related to a higher chance of identifying a PV. (4) Conclusions: In our cohort, which was enriched with families with a high number of BC cases, a high proportion of mutations in ATM and CHEK2 were identified. The clinical characteristics of BC associated with moderate-risk genes were different from those related to BRCA1/2 genes.
Entities:
Keywords:
BRCA1 or BRCA2 negative; germline testing; hereditary breast and ovarian cancer; moderate penetrance genes; next-generation sequencing
Authors: María Molina-Zayas; Carmen Garrido-Navas; Jose Luis García-Puche; Julian Barwell; Susana Pedrinaci; Margarita Martínez Atienza; Susana García-Linares; Tomás de Haro-Muñoz; Jose Antonio Lorente; M Jose Serrano; Antonio Poyatos-Andújar Journal: Mol Genet Genomics Date: 2022-04-22 Impact factor: 2.980
Authors: Marcella Nunziato; Federica Di Maggio; Matilde Pensabene; Maria Valeria Esposito; Flavio Starnone; Carmine De Angelis; Alessandra Calabrese; Massimiliano D'Aiuto; Gerardo Botti; Sabino De Placido; Valeria D'Argenio; Francesco Salvatore Journal: Front Med (Lausanne) Date: 2022-08-11