• Marta Rodríguez-Balada, Bàrbara Roig, Mireia Melé, Cinta Albacar, Sara Serrano, Mònica Salvat, Montserrat Querol, Joan Borràs, Lourdes Martorell, and Josep Gumà.
• Institut d'Oncologia de la Catalunya Sud (IOCS), Hospital Universitari Sant Joan de Reus, Àrea d'Oncologia, Av. Del Dr. Josep Laporte, 43204, Reus, Spain; Universitat Rovira i Virgili, Departament de Medicina i Cirurgia, Spain; Institut d'Investigació Sanitària Pere Virgili, IISPV, Spain. Electronic address: mrodriguez@grupsagessa.cat.
• Clin. Biochem. 2020 Feb 1; 76: 17-23.

BackgroundApproximately 5-10% of breast carcinomas have been related to hereditary conditions and are attributable to pathogenic variants in the BRCA1 and BRCA2 genes, which is referred to as hereditary breast and ovarian cancer (HBOC) syndrome. The inclusion of additional genes that can be related to HBOC syndrome is under intense evaluation due to the high proportion of patients with HBOC criteria who do not present pathogenic mutations in BRCA genes, named BRCAX, despite having high clinical suspicion of hereditary cancer. The main aim is to identify new potentially pathogenic gene variants that may contribute to HBOC to improve the efficiency of routine diagnostic tests in this hereditary condition.MethodsA retrospective cohort of 77 HBOC BRCAX patients was analyzed by next-generation sequencing using a targeted multigene panel composed of 25 genes related to hereditary cancer and deficiencies in DNA repair pathways.ResultsWe found 9 variants in 7 different genes, which were confirmed by automated sequencing. Six variants were classified as pathogenic or likely pathogenic. Three of them were located in the PALB2 gene, one in the BRIP1 gene, one in the BARD1 gene and 1 in the RAD50 gene. In addition, three variants of uncertain significance (VUS) were detected in the TP53, CHEK2, and CDH1 genes.ConclusionsWe identified that 8% of BRCAX patients were carriers of pathogenic variants in genes other than BRCA1 and BRCA2. Therefore, wide gene panels, including clinically actionable genes, should be routinely used in the screening of HBOC in our population. We observed differences from other studies in the prevalence of mutated genes, most likely due to differences in the selection criteria of the probands and in the population analyzed. The high incidence of deleterious variant detection in PALB2 supports its significant role in breast cancer susceptibility and reinforces its inclusion in the HBOC genetic diagnostic process.Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

24 keywords...

hide…