Pancreas. 2022 Apr 1;51(4):302-304. doi: 10.1097/MPA.0000000000002021. Epub 2022 Jun 11.
Germline genetic testing is universally recommended for patients with pancreatic cancer to guide therapeutic selection, but tumor molecular profiling (TMP) is not. We aimed to determine the real-world additional diagnostic benefit of TMP after germline testing for detecting therapeutically actionable alterations.
Medical records and genetic test reports were reviewed for all patients who underwent germline testing and TMP at the University of California San Francisco during January 2016-January 2020. The detection rate of actionable alterations with germline testing alone was compared to that with both germline testing and TMP.
Among 738 eligible patients, 144 (20%) met study criteria. Germline testing detected 10 actionable alterations in 10 patients. Tumor molecular profiling identified 3 new therapeutic targets among these 10 patients and 45 targets in 41 additional patients, increasing the number of patients with actionable findings from 10 (7%) to 51 (35%). Most actionable alterations (35/58, 60%) involved genes associated with the Homologous Recombination DNA Damage Repair pathway.
Tumor molecular profiling after germline testing increased the detection of actionable alterations by 5-fold. Tumor molecular profiling is a necessary complement to germline genetic testing to fully inform therapeutic decision making for all patients with pancreatic cancer.
对胰腺癌患者进行种系基因检测以指导治疗选择已得到广泛推荐，但肿瘤分子谱分析（TMP）并非如此。我们旨在确定种系基因检测后进行 TMP 的实际附加诊断益处，以检测治疗相关的可改变。
对 2016 年 1 月至 2020 年 1 月期间在加利福尼亚大学旧金山分校接受种系基因检测和 TMP 的所有患者的病历和基因检测报告进行了回顾性分析。比较单独进行种系基因检测与同时进行种系基因检测和 TMP 时可检测到的治疗性改变的检测率。
在 738 名符合条件的患者中，有 144 名（20%）符合研究标准。种系基因检测在 10 名患者中发现了 10 个可改变的治疗靶点。TMP 在这 10 名患者中发现了 3 个新的治疗靶点，在另外 41 名患者中发现了 45 个治疗靶点，将可检测到的治疗靶点的患者数量从 10 名（7%）增加到 51 名（35%）。大多数可改变的治疗靶点（35/58，60%）涉及与同源重组 DNA 损伤修复途径相关的基因。
种系基因检测后进行 TMP 可将可改变治疗靶点的检测率提高 5 倍。TMP 是种系基因检测的必要补充，可全面告知所有胰腺癌患者的治疗决策。
