Noncoding RNA Expression and Targeted Next-Generation Sequencing Distinguish Tubulocystic Renal Cell Carcinoma (TC-RCC) from Other Renal Neoplasms

J Mol Diagn. 2018 Jan;20(1):34-45. doi: 10.1016/j.jmoldx.2017.09.002. Epub 2017 Oct 19.

Abstract

Tubulocystic renal cell carcinoma (TC-RCC) is a rare recently described renal neoplasm characterized by gross, microscopic, and immunohistochemical differences from other renal tumor types and was recently classified as a distinct entity. However, this distinction remains controversial particularly because some genetic studies suggest a close relationship with papillary RCC (PRCC). The molecular basis of this disease remains largely unexplored. We therefore performed noncoding (nc) RNA/miRNA expression analysis and targeted next-generation sequencing mutational profiling on 13 TC-RCC cases (11 pure, two mixed TC-RCC/PRCC) and compared with other renal neoplasms. The expression profile of miRNAs and other ncRNAs in TC-RCC was distinct and validated 10 differentially expressed miRNAs by quantitative RT-PCR, including miR-155 and miR-34a, that were significantly down-regulated compared with PRCC cases (n = 22). With the use of targeted next-generation sequencing we identified mutations in 14 different genes, most frequently (>60% of TC-RCC cases) in ABL1 and PDFGRA genes. These mutations were present in <5% of clear cell RCC, PRCC, or chromophobe RCC cases (n > 600) of The Cancer Genome Atlas database. In summary, this study is by far the largest molecular study of TC-RCC cases and the first to investigate either ncRNA expression or their genomic profile. These results add molecular evidence that TC-RCC is indeed a distinct entity from PRCC and other renal neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Diagnosis, Differential
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mutation / genetics
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Reproducibility of Results

Substances

  • MicroRNAs
  • RNA, Untranslated