Hakimi A Ari, Attalla Kyrollis, DiNatale Renzo G, Ostrovnaya Irina, Flynn Jessica, Blum Kyle A, Ged Yasser, Hoen Douglas, Kendall Sviatoslav M, Reznik Ed, Bowman Anita, Hwee Jason, Fong Christopher J, Kuo Fengshen, Voss Martin H, Chan Timothy A, Motzer Robert J
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Commun. 2020 Aug 20;11(1):4168. doi: 10.1038/s41467-020-17965-0.
There is conflicting data regarding the role of PBAF complex mutations and response to immune checkpoint blockade (ICB) therapy in clear cell renal cell carcinoma (ccRCC) and other solid tumors. We assess the prevalence of PBAF complex mutations from two large cohorts including the pan-cancer TCGA project (n = 10,359) and the MSK-IMPACT pan-cancer immunotherapy cohort (n = 3700). Across both cohorts, PBAF complex mutations, predominantly PBRM1 mutations, are most common in ccRCC. In multivariate models of ccRCC patients treated with ICB (n = 189), loss-of-function (LOF) mutations in PBRM1 are not associated with overall survival (OS) (HR = 1.24, p = 0.47) or time to treatment failure (HR = 0.85, p = 0.44). In a series of 11 solid tumors (n = 2936), LOF mutations are not associated with improved OS in a stratified multivariate model (HR = 0.9, p = 0.7). In a current series of solid tumors treated with ICB, we are unable to demonstrate favorable response to ICB in patients with PBAF complex mutations.
关于PBAF复合物突变在透明细胞肾细胞癌（ccRCC）和其他实体瘤中对免疫检查点阻断（ICB）治疗反应的作用，存在相互矛盾的数据。我们评估了来自两个大型队列的PBAF复合物突变的患病率，包括泛癌TCGA项目（n = 10359）和MSK-IMPACT泛癌免疫治疗队列（n = 3700）。在这两个队列中，PBAF复合物突变，主要是PBRM1突变，在ccRCC中最为常见。在接受ICB治疗的ccRCC患者的多变量模型中（n = 189），PBRM1中的功能丧失（LOF）突变与总生存期（OS）（HR = 1.24，p = 0.47）或治疗失败时间（HR = 0.85，p = 0.44）无关。在一系列11种实体瘤（n = 2936）中，在分层多变量模型中，LOF突变与改善的OS无关（HR = 0.9，p = 0.7）。在目前接受ICB治疗的一系列实体瘤中，我们无法证明PBAF复合物突变患者对ICB有良好反应。
