Background: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined. Patients and Methods: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care®protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.5 mg/dL prior to RCC diagnosis. Results: Of 296 patients with RCC, 61 met the criteria for ACKD. The most common somatic mutations in the overall cohort were inVHL(126, 42.6%),PBRM1(102, 34.5%), andSETD2(54, 18.2%).BAP1had a decreased mutational frequency in RCC specimens from patients without ACKD as compared to those with ACKD (10.6% versus 1.6%), but this was not statistically significant in univariable (OR 0.14,p= 0.056) or multivariable (OR 0.15,p= 0.067) analysis. Median OS was not reached in either cohort. Conclusions: Using the clinicogenomic ORIEN database, our study found lower rates ofBAP1mutations in RCC specimens from patients with ACKD, which may reflect aBAP1-independent mutational driver of RCC in patients with ACKD.
背景：晚期慢性肾脏病（ACKD）患者罹患肾细胞癌（RCC）的风险增高，但ACKD相关RCC标本的分子改变及患者总生存期（OS）尚未明确。患者与方法：通过肿瘤研究信息交换网络（ORIEN）的"全面癌症照护"协议，纳入296例经知情同意、接受体细胞肿瘤全外显子组测序的成年RCC患者。ACKD定义为RCC诊断前血清肌酐≥1.5 mg/dL的患者。结果：在296例RCC患者中，61例符合ACKD标准。全队列最常见的体细胞突变基因为VHL（126例，42.6%）、PBRM1（102例，34.5%）和SETD2（54例，18.2%）。与ACKD患者相比，非ACKD患者RCC标本中BAP1突变频率降低（10.6%对比1.6%），但在单变量（OR 0.14，p=0.056）或多变量（OR 0.15，p=0.067）分析中均未达到统计学显著性。两组患者的中位OS均未达到。结论：通过临床基因组学ORIEN数据库，本研究发现ACKD患者RCC标本中BAP1突变率较低，这可能提示ACKD患者存在不依赖BAP1的RCC突变驱动机制。
肿瘤(癌症)患者之家