MicroRNA expression profiling of Xp11 renal cell carcinoma.

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MicroRNA expression profiling of Xp11 renal cell carcinoma.

Hum Pathol. 2017 Apr 11;:

Authors: Marchionni L, Hayashi M, Guida E, Ooki A, Munari E, Jabboure FJ, Dinalankara W, Raza A, Netto GJ, Hoque MO, Argani P

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 1-4% of adult cases, frequently displaying papillary architecture with epithelioid clear cells. In order to better understand the biology of this molecularly distinct tumor subtype, we analyze the miRNA expression profiles of Xp11 Renal cell carcinoma (RCC) compared to normal renal parenchyma using microarray and quantitative reverse transcription polymerase chain reaction (RT-PCR). We further compare Xp11 RCC with other RCC histologic subtypes using publically available datasets, identifying common and distinctive microRNA (miRNA) signatures along with the associated signaling pathways and biological processes. Overall, Xp11 RCC more closely resemble clear cell rather than papillary RCC. Further, 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, while miR-133b and miR-658 were down-regulated. Finally, Xp11 RCC is most strongly associated with microRNA 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.

PMID: 28411178 [PubMed - as supplied by publisher]

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