Winston-Salem, 27104 NC, USA.
Clin Lung Cancer. 2022 Nov;23(7):e405-e407. doi: 10.1016/j.cllc.2022.07.011. Epub 2022 Jul 21.
Tumor next generation sequencing (NGS) is used to interrogate nearly every non-small cell lung cancer (NSCLC) for the purpose of identifying actionable genetic alterations. Occasionally, tumor NGS also uncovers "incidental" apparent pathogenic germline variants (PGVs), with BRCA2 being among the most common of those. If germline testing confirms a BRCA2 PGV in a patient with NSCLC, therapies targeting that BRCA2 PGV might be considered, if the patient has exhausted standard NSCLC therapeutic options. Surveillance and preventive therapies for BRCA2-related cancers would be recommended or considered for that patient, as well as for family members found to carry that same BRCA2 PGV. Here, I offer my perspective related to the evidence supporting and against germline testing in patients with NSCLCs that show incidental BRCA2 apparent PGVs. I use an example to underscore how important it is to explain to patients, before tumor NGS, the possibility of uncovering an incidental PGV. I also review the myriad uncertainties related to identifying a BRCA2 PGV, when the sole indication for germline testing was the uncovering of the incidental BRCA2 apparent PGV.
肿瘤下一代测序（NGS）用于检测几乎所有非小细胞肺癌（NSCLC），以确定可采取的遗传改变。偶尔，肿瘤 NGS 还会发现“偶然”的明显致病性种系变异（PGV），其中 BRCA2 是最常见的种系变异之一。如果种系检测在 NSCLC 患者中证实存在 BRCA2 PGV，则可以考虑针对该 BRCA2 PGV 的治疗方法，如果患者已经用尽了标准的 NSCLC 治疗选择。还会建议或考虑对该患者以及发现携带相同 BRCA2 PGV 的家庭成员进行 BRCA2 相关癌症的监测和预防治疗。在这里，我提供了我对支持和反对在显示偶然 BRCA2 明显 PGV 的 NSCLC 患者中进行种系检测的证据的看法。我使用一个例子强调了在进行肿瘤 NGS 之前，向患者解释发现偶然 PGV 的可能性是多么重要。我还回顾了在仅因偶然发现 BRCA2 明显 PGV 而进行种系检测的情况下，确定 BRCA2 PGV 时存在的无数不确定性。
