Genomic profiling of renal cell carcinoma in patients with end-stage renal disease

本研究的目的是通过分析基因组拷贝数畸变（CNAs）来确定终末期肾病肾细胞癌（RCC-ESRD）的基因组谱。采用Agil ent全人类基因组4×44K Oligo微阵列，对63例RCC-ESRD患者的79份肿瘤样本进行了阵列比较基因组杂交（array CGH）分析。无监督分层聚类分析显示，63例病例可分为两组：A组和B组。A组主要由透明细胞RCCs （CCRCCs）组成，而B组主要由乳头状RCCs （PRCCs）、获得性囊性疾病（ACD）相关的RCCs和透明细胞乳头状RCCs组成。平均频率分析显示，聚类A和B的基因组图谱分别与散发性CCRCC和散发性乳头状RCC （PRCC）相似。尽管在组织病理学的基础上，已经提出acd相关的RCC、透明细胞乳头状RCC和PRCC-ESRD是不同的亚型，但我们目前的数据显示，它们的基因组图谱被归类为B群，彼此相似。此外，PRCC、acd相关RCC和透明细胞乳头状RCC混合在一个组织中的基因组图谱趋于相似。基于RCC-ESRD的基因组分析，我们认为CCRCC- esrd的分子发病机制与散发性CCRCC相似。尽管非ccrcc - esrd的各种组织学亚型已经被提出，但它们的基因组谱与散发性PRCC相似，这表明非ccrcc - esrd的分子发病机制可能与散发性PRCC有关。

The purpose of this study was to determine the genomic profile of renal cell carcinoma in end-stage renal disease (RCC-ESRD) by analysis of genomic copy number aberrations (CNAs). Seventy-nine tumor samples from 63 patients with RCC-ESRD were analyzed by array comparative genomic hybridization (array CGH) using the Agil ent Whole Human Genome 4×44K Oligo Micro Array. Unsupervised hierarchical clustering analysis revealed that the 63 cases were divisible into two groups: clusters A and B. Cluster A comprised mainly clear cell RCCs (CCRCCs), whereas cluster B comprised mainly papillary RCCs (PRCCs), acquired cystic disease (ACD)-associated RCCs and clear cell papillary RCCs. Analysis of the averaged frequencies revealed that the genomic profiles of clusters A and B resembled those of sporadic CCRCC and sporadic papillary RCC (PRCC), respectively. Although, on the basis of histopathology, it has been proposed that ACD-associated RCC, clear cell papillary RCC and PRCC-ESRD are distinct subtypes, our present data reveal that their genomic profiles categorized as cluster B resemble one another. Furthermore, genomic profiles of PRCC, ACD-associated RCC and clear cell papillary RCC admixed in one tissue tended to resemble one another. On the basis of genomic profiling of RCC-ESRD, we conclude that the molecular pathogenesis of CCRCC-ESRD resembles that of sporadic CCRCC. Although various histologic subtypes of non-CCRCC-ESRD have been proposed, their genomic profiles resemble those of sporadic PRCC, suggesting that the molecular pathogenesis of non-CCRCC-ESRD might be related to that of sporadic PRCC.