Fanale Daniele, Fiorino Alessia, Incorvaia Lorena, Dimino Alessandra, Filorizzo Clarissa, Bono Marco, Cancelliere Daniela, Calò Valentina, Brando Chiara, Corsini Lidia Rita, Sciacchitano Roberta, Magrin Luigi, Pivetti Alessia, Pedone Erika, Madonia Giorgio, Cucinella Alessandra, Badalamenti Giuseppe, Russo Antonio, Bazan Viviana
Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, Palermo, Italy.
Front Oncol. 2021 Jun 11;11:682445. doi: 10.3389/fonc.2021.682445. eCollection 2021.
About 10-20% of breast/ovarian (BC/OC) cancer patients undergoing germline genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the "Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors" of University Hospital Policlinico "P. Giaccone" of Palermo, were genetically tested for germline variants through Next-Generation Sequencing analysis. The mutational screening showed that 639 (73.1%) out of 874 patients were -, whereas 67 (7.7%) were carriers of germline VUSs, and 168 (19.2%) harbored germline pathogenic/likely pathogenic variants. Our analysis revealed the presence of 59 different VUSs detected in 67 patients, 46 of which were affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on gene, whereas 38 (64.4%) on . We detected six alterations in and two in with unclear interpretation of clinical significance. Familial anamnesis of a patient harboring the -c.3367G>T suggests for this variant a potential of pathogenicity, therefore it should be carefully investigated. Understanding clinical significance of germline VUS could improve, in future, the identification of potentially high-risk variants useful for clinical management of BC or OC patients and family members.
接受种系基因检测的乳腺癌/卵巢癌（BC/OC）患者中，约10%-20%被发现携带意义未明的变异（VUS）。由于对意大利南部种系VUS的患病率了解甚少，我们的研究旨在描述在BC/OC患者中检测到的这些变异的谱，以改善对有助于患者临床管理的潜在高危变异的识别。2016年10月至2020年12月期间，在巴勒莫大学医院“P.贾科内”综合医院的“西西里地区罕见和遗传家族性肿瘤预防、诊断和治疗中心”登记的874例BC或OC患者，通过下一代测序分析对种系变异进行了基因检测。突变筛查显示，874例患者中有639例（73.1%）为阴性，而67例（7.7%）是种系VUS的携带者，168例（19.2%）携带种系致病/可能致病变异。我们的分析揭示了在67例患者中检测到59种不同的VUS，其中46例受BC影响，21例受OC影响。59种变异中有21种（35.6%）位于基因上，而38种（64.4%）位于上。我们在中检测到6种改变，在中有2种改变，其临床意义的解释尚不清楚。携带-c.3367G>T的患者的家族史提示该变异具有潜在的致病性，因此应仔细研究。了解种系VUS的临床意义未来可能会改善对有助于BC或OC患者及其家庭成员临床管理的潜在高危变异的识别。
