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（CNA）来确定终末期肾病肾细胞癌（RCC-ESRD）的基因组谱。采用Agilent全人类基因组4× 44 K寡核苷酸微阵列对63例RCC-ESRD患者的79例肿瘤标本进行比较基因组杂交（array CGH）分析。无监督系统聚类分析显示63例可分为两组：A组和B组。簇A主要包括透明细胞RCC（CCRCC），而簇B主要包括乳头状RCC（PRCC）、获得性囊性病（ACD）相关RCC和透明细胞乳头状RCC。平均频率分析显示，簇A和B的基因组图谱分别类似于散发性CCRCC和散发性乳头状RCC（PRCC）。虽然，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，我们目前的数据显示，它们的基因组图谱归类为集群B彼此相似。此外，混合在一种组织中的PRCC、ACD相关RCC和透明细胞乳头状RCC的基因组谱倾向于彼此相似。基于RCC-ESRD的基因组分析，我们得出结论，CCRCC-ESRD的分子发病机制类似于散发性CCRCC。虽然已经提出了非CCRCC-ESRD的各种组织学亚型，但它们的基因组谱与散发性PRCC相似，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.