Asmann Yan W, Parikh Kaushal, Bergsagel P Leif, Dong Haidong, Adjei Alex A, Borad Mitesh J, Mansfield Aaron S
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
Precision Cancer Therapeutics of Mayo Clinic's Center for Individualized Medicine, Rochester, MN, USA.
NPJ Precis Oncol. 2021 Mar 19;5(1):22. doi: 10.1038/s41698-021-00164-5.
With the recent FDA approval of tumor mutational burden-high (TMB-H) status as a biomarker for treatment with a PD-1 inhibitor regardless of tumor type, accurate assessment of patient-specific TMB is more critical now more than ever. Using paired tumor and germline exome sequencing data from 701 patients newly diagnosed with multiple myeloma, including 575 self-reported White patients and 126 self-reported Black patients, we observed that compared to the gold standard of filtering germline variants with patient-paired germline sequencing data, TMB estimates were significantly higher in both Black and White patients when using public databases for filtering non-somatic mutations; however, TMB was more significantly inflated in Black patients compared to White patients. TMB as a biomarker for patient selection to receive immune checkpoint inhibitors (ICIs) therapy without patient-paired germline sequencing may introduce racial bias due to the under-representation of minority groups in public databases.
随着美国食品药品监督管理局（FDA）最近批准将肿瘤突变负荷高（TMB-H）状态作为一种生物标志物，用于无论肿瘤类型如何均可接受PD-1抑制剂治疗的患者，现在比以往任何时候都更需要准确评估患者特异性TMB。利用来自701例新诊断为多发性骨髓瘤患者的配对肿瘤和种系外显子组测序数据，包括575例自我报告为白人的患者和126例自我报告为黑人的患者，我们观察到，与使用患者配对种系测序数据筛选种系变异的金标准相比，在使用公共数据库筛选非体细胞突变时，黑人和白人患者的TMB估计值均显著更高；然而，与白人患者相比，黑人患者的TMB膨胀更为显著。在没有患者配对种系测序的情况下，将TMB作为选择接受免疫检查点抑制剂（ICI）治疗患者的生物标志物，可能会由于公共数据库中少数群体代表性不足而导致种族偏见。
