Cancers, Vol. 11, Pages 522: Germline Missense Variants in BRCA1: New Trends and Challenges for Clinical Annotation

Cancers, Vol. 11, Pages 522: Germline Missense Variants in BRCA1: New Trends and Challenges for Clinical Annotation Cancers doi: 10.3390/cancers11040522 Authors: Volha A. Golubeva Thales C. Nepomuceno Alvaro N. A. Monteiro Genetic testing allows for the identification of germline DNA variations, which are associated with a significant increase in the risk of developing breast cancer (BC) and ovarian cancer (OC). Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with the PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for the annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision-making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as variants of uncertain clinical significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of va...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research