Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy.
Department of Radiotherapy, San Giovanni di Dio Hospital, ASP of Agrigento, Agrigento, Italy.
Crit Rev Oncol Hematol. 2022 Apr;172:103626. doi: 10.1016/j.critrevonc.2022.103626. Epub 2022 Feb 10.
Hereditary breast and ovarian cancer syndrome is caused by germline mutations in BRCA1/2 genes. These genes are very large and their mutations are heterogeneous and scattered throughout the coding sequence. In addition to the above-mentioned mutations, variants of uncertain/unknown significance (VUSs) have been identified in BRCA genes, which make more difficult the clinical management of the patient and risk assessment. In the last decades, several laboratories have developed different databases that contain more than 2000 variants for the two genes and integrated strategies which include multifactorial prediction models based on direct and indirect genetic evidence, to classify the VUSs and attribute them a clinical significance associated with a deleterious, high/low or neutral risk. This review provides a comprehensive overview of literature studies concerning the VUSs, in order to assess their impact on the population and provide new insight useful for the appropriate patient management in clinical practice.
遗传性乳腺癌和卵巢癌综合征是由 BRCA1/2 基因的种系突变引起的。这些基因非常大，其突变具有异质性且分散在编码序列中。除了上述突变外，BRCA 基因中还发现了意义不确定/未知的变异体（VUS），这使得患者的临床管理和风险评估更加困难。在过去的几十年中，几家实验室已经开发了不同的数据库，其中包含了这两个基因的 2000 多个变体，并整合了多种策略，包括基于直接和间接遗传证据的多因素预测模型，以对 VUS 进行分类，并将其归因于与有害、高/低或中性风险相关的临床意义。本综述全面概述了有关 VUS 的文献研究，以评估它们对人群的影响，并为临床实践中对患者的适当管理提供新的见解。
