MicroRNA expression profiling of Xp11 renal cell carcinoma

Hum Pathol. 2017 Sep:67:18-29. doi: 10.1016/j.humpath.2017.03.011. Epub 2017 Apr 12.


Renal cell carcinomas (RCCs) with Xp11 translocation (Xp11 RCC) constitute a distinctive molecular subtype characterized by chromosomal translocations involving the Xp11.2 locus, resulting in gene fusions between the TFE3 transcription factor with a second gene (usually ASPSCR1, PRCC, NONO, or SFPQ). RCCs with Xp11 translocations comprise up to 1% to 4% of adult cases, frequently displaying papillary architecture with epithelioid clear cells. To better understand the biology of this molecularly distinct tumor subtype, we analyze the microRNA (miRNA) expression profiles of Xp11 RCC compared with normal renal parenchyma using microarray and quantitative reverse-transcription polymerase chain reaction. We further compare Xp11 RCC with other RCC histologic subtypes using publically available data sets, identifying common and distinctive miRNA signatures along with the associated signaling pathways and biological processes. Overall, Xp11 RCC more closely resembles clear cell rather than papillary RCC. Furthermore, among the most differentially expressed miRNAs specific for Xp11 RCC, we identify miR-148a-3p, miR-221-3p, miR-185-5p, miR-196b-5p, and miR-642a-5p to be up-regulated, whereas miR-133b and miR-658 were down-regulated. Finally, Xp11 RCC is most strongly associated with miRNA expression profiles modulating DNA damage responses, cell cycle progression and apoptosis, and the Hedgehog signaling pathway. In summary, we describe here for the first time the miRNA expression profiles of a molecularly distinct type of renal cancer associated with Xp11.2 translocations involving the TFE3 gene. Our results might help understanding the molecular underpinning of Xp11 RCC, assisting in developing targeted treatments for this disease.

Keywords: Analysis of Functional Annotation; Renal cell carcinoma; TFE3 gene fusion; Xp11 translocation; gene regulation; microRNA expression profiling.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy
  • Child
  • Child, Preschool
  • Chromosomes, Human, X*
  • Computational Biology
  • Databases, Genetic
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Prognosis
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome
  • Translocation, Genetic*


  • Biomarkers, Tumor
  • MicroRNAs