Bekos Christine, Grimm Christoph, Kranawetter Marlene, Polterauer Stephan, Oberndorfer Felicitas, Tan Yen, Müllauer Leonhard, Singer Christian F
Comprehensive Cancer Center, Gynecologic Cancer Unit, Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, A-1090 Vienna, Austria.
Department of Pathology, Medical University of Vienna, A-1090 Vienna, Austria.
J Pers Med. 2021 Jun 24;11(7):593. doi: 10.3390/jpm11070593.
BRCA 1/2 mutation status has become one of the most important parameters for treatment decision in patients with epithelial ovarian cancer (EOC). The aim of this study was to compare tumor DNA with blood DNA sequencing to evaluate the reliability of BRCA tumor testing results.
Patients who were treated for EOC between 2003 and 2019 at the Medical University of Vienna and underwent both germline (gBRCA) and tumor (tBRCA) testing for BRCA mutations were identified. We calculated the concordance rate and further analyzed discordant cases.
Out of 140 patients with EOC, gBRCA mutation was found in 47 (33.6%) and tBRCA mutation in 53 (37.9%) patients. Tumor testing identified an additional 9/140 (6.4%) patients with somatic BRCA mutation and negative germline testing. The comparison of germline testing with tumor testing revealed a concordance rate of 93.5% and a negative predictive value of tumor testing of 96.0%. After BRCA variants of uncertain significance were included in the analysis, concordance rate decreased to 90.9%.
Tumor testing identified the majority of pathogenic germline BRCA mutations but missed three (2.1%) patients. In contrast, nine (6.4%) patients harboring a somatic BRCA mutation would have been missed by gBRCA testing only.
BRCA 1/2突变状态已成为上皮性卵巢癌（EOC）患者治疗决策的最重要参数之一。本研究的目的是比较肿瘤DNA与血液DNA测序，以评估BRCA肿瘤检测结果的可靠性。
确定2003年至2019年在维也纳医科大学接受EOC治疗并接受BRCA突变的种系（gBRCA）和肿瘤（tBRCA）检测的患者。我们计算了一致性率，并进一步分析了不一致的病例。
在140例EOC患者中，47例（33.6%）发现gBRCA突变，53例（37.9%）发现tBRCA突变。肿瘤检测还发现另外9/140例（6.4%）患者存在体细胞BRCA突变且种系检测为阴性。种系检测与肿瘤检测的比较显示一致性率为93.5%，肿瘤检测的阴性预测值为96.0%。将意义不明确的BRCA变异纳入分析后，一致性率降至90.9%。
肿瘤检测识别出了大多数致病性种系BRCA突变，但遗漏了3例（2.1%）患者。相比之下，仅进行gBRCA检测会遗漏9例（6.4%）携带体细胞BRCA突变的患者。
