Which cytogenetic findings are characteristic of translocation-associated renal cell carcinomas (RCCs)?

Updated: May 17, 2017
  • Author: Angela J Wu, MD; Chief Editor: Liang Cheng, MD  more...
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Translocation carcinomas most commonly harbor either t(X;17)(p11.2;q25), which leads to a fusion of the transcription factor gene TFE3 with the ASPL gene; t(X;1)(p11.2;p34), which leads to the fusion of the TFE3 gene with the PSF gene; or t(X;1)(p11.2;q21), which leads to a fusion of the TFE3 gene with the PRCC gene.

Other, less commonly described translocations in these renal cell carcinomas (RCCs) include inv (X)(p11;q12), which leads to a fusion of the TFE3 gene to the NonO (p54nrb) gene, and t(X;17)(p11.2;q23), which leads to the fusion of the TFE gene to the CLTC gene. [2, 10, 21, 22]

Transcription factor EB (TFEB) RCCs are characterized by a translocation between the alpha gene at 11q12 and the first intron of the TFEB transcription factor gene at 6p21. [2, 16]

TFE3 and TFEB, along with TFEC and MiTF, are members of the microphthalmia-associated transcription factor (MiTF) family, which have homologous deoxyribonucleic acid (DNA) binding sequences. MiTF is probably the best characterized member of this family; it is known to play an important role in melanocyte, mast cell, and eye development. Deregulation of this gene is also thought to be crucial in the development of melanocytic tumors. Although the exact pathogenesis underlying translocation-associated RCC is not known, it has been speculated that loss of downstream target gene expression and loss of cell cycle regulation play key roles. [2, 22]

A genome-wide study defined the incidence of translocation renal cell carcinoma (TRCC) within a clear-cell RCC-directed project and expanded the genomic spectrum of TRCC by identifying novel MITF/TFE partners involved in RNA splicing and frequent mutations in chromatin-remodeling genes. [23]

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