Department of Urology, University of Michigan Medical School.
Rogel Cancer Center, Michigan Medicine.
Curr Opin Urol. 2018 Jul;28(4):383-391. doi: 10.1097/MOU.0000000000000516.
Large-scale genomic profiling has shed new light on the molecular underpinnings of renal cell carcinoma (RCC), spurring a much needed refinement of RCC subclassification based on an integrative assessment of histopathologic features and molecular alterations. At the same time, renal mass biopsies have become increasingly commonplace, necessitating ancillary tools to help guide clinical management. Herein, we briefly review our current understanding of RCC genomics, highlighting areas of possible clinical utility, as well as potential limitations, for renal mass biopsies.
Distinct RCC subtypes harbor characteristic molecular features, including somatic mutations, copy number alterations, and genomic rearrangements. Existing ancillary tools, including fluorescent in-situ hybridization and immunohistochemistry, may be useful for diagnostic subclassification. Recurrent secondary molecular alterations in clear cell RCC (BAP1, SETD2, PBRM1, and TP53) and papillary RCC (CDKN2A) may be associated with poor prognosis; however, intratumoral genomic heterogeneity may limit the clinical utility of these molecular biomarkers in renal mass biopsies.
Recent technological advances have the potential to fundamentally alter the clinical management of RCC by leveraging our increasing understanding of RCC genomics to assess hundreds of molecular biomarkers simultaneously. Additional focused molecular analyses of renal mass biopsy cohorts are needed prior to widespread implementation of molecular biomarker assays.
大规模基因组分析揭示了肾细胞癌（RCC）的分子基础，这促使我们需要根据组织病理学特征和分子改变的综合评估，对 RCC 进行更精细的分类。与此同时，肾肿瘤活检越来越普遍，需要辅助工具来帮助指导临床管理。本文简要回顾了我们对 RCC 基因组学的现有认识，重点介绍了肾肿瘤活检中可能具有临床应用价值的领域，以及潜在的局限性。
不同的 RCC 亚型具有特征性的分子特征，包括体细胞突变、拷贝数改变和基因组重排。现有的辅助工具，包括荧光原位杂交和免疫组织化学，可能对诊断亚分类有用。透明细胞 RCC（BAP1、SETD2、PBRM1 和 TP53）和乳头状 RCC（CDKN2A）中复发性的次要分子改变可能与预后不良有关；然而，肿瘤内基因组异质性可能限制这些分子生物标志物在肾肿瘤活检中的临床应用。
最近的技术进步有可能通过利用我们对 RCC 基因组学的日益了解，同时评估数百种分子生物标志物，从根本上改变 RCC 的临床管理。在广泛实施分子生物标志物检测之前，需要对肾肿瘤活检队列进行更有针对性的分子分析。
