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

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.

• Authors: Charles H Lawrie, María Armesto, Marta Fernandez-Mercado, María Arestín, Lorea Manterola, Ibai Goicoechea, Erika Larrea, María M Caffarel, Angela M Araujo, Carla Sole, Maris Sperga, Isabel Alvarado-Cabrero, Michal Michal, Ondrej Hes, José I López
• Journal: The Journal of molecular diagnostics : JMD (J Mol Diagn) Vol. 20 Issue 1 Pg. 34-45 (01 2018) ISSN: 1943-7811 [Electronic] United States
• PMID: 29056573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• MicroRNAs
• RNA, Untranslated

Topics

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