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

MicroRNA expression profiling of Xp11 renal cell carcinoma.

Author information

1
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Center for Computational Genomics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: marchion@jhu.edu.
2
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
3
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
4
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, Sacro Cuore Hospital Negrar, Verona 37024, Italy.
5
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, University of Alabama School of Medicine, Birmingham, AL 35233, USA.
6
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
7
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: pargani@jhmi.edu.

Abstract

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

PMID:
28411178
PMCID:
PMC5628161
DOI:
10.1016/j.humpath.2017.03.011
[Indexed for MEDLINE]
Free PMC Article

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