Translocation-Associated Renal Cell Carcinoma (TRCC)

Overview

Translocation-Associated Renal Cell Carcinoma (TRCC) is defined by chromosomal translocations involving MiTF/TFE family members (TFE3, TFEB, MITF), producing gene fusions that drive oncogenesis. It sits under NCCRCC in OncoTree (tissue: Kidney) and may be diagnostically challenging to distinguish from other nccRCC subtypes.

Cohorts in the corpus

  • nccrcc_genentech_2014 — 6 translocation RCC tumors profiled by whole-exome sequencing, RNA-seq, and SNP copy-number arrays; two additional unclassified cases were reclassified as tRCC after genomic analysis PMID:25401301.

Recurrent alterations

  • In 6 tRCCs, known ASPSCR1-TFE3 and PRCC-TFE3 fusions were confirmed by FISH; a novel CLTC-TFEB in-frame fusion was identified in one unclassified case reclassified as tRCC; a novel MIDN-SBNO2 fusion (chr19p13.3 inversion) was found in a TFE3-fusion-negative case, driving elevated SBNO2 expression PMID:25401301.
  • Two tRCC cases showed elevated TFE3 expression without detectable TFE3 fusion or amplification, indicating additional mechanisms of TFE3 activation beyond canonical translocation PMID:25401301.
  • MiTF-family translocation tumors (TFE3/TFEB IHC/FISH positive) were prospectively excluded from the URCC cohort (n=62, MSKCC), confirming TRCC as a distinct entity; URCC T12 carries a TPM3-ALK fusion representing a separate non-TFE3/TFEB translocation-driven entity PMID:27713405.

Subtypes

  • MiTF-high subtype: tumors with MiTF/TFE3/TFEB fusions or amplifications consistently overexpress BIRC7, an anti-apoptotic MITF target gene proposed as a diagnostic and therapeutic marker PMID:25401301.

Therapeutic landscape

  • BIRC7 overexpression in MiTF-fusion tumors is proposed as a therapeutic vulnerability PMID:25401301.
  • TFEB amplification (beyond translocation) expands the set of tRCC cases for whom TFEB-targeted strategies may apply PMID:25401301.

Sources

  • PMID:25401301 — Durinck et al., integrated genomic profiling of 167 non-clear cell RCCs including 6 tRCCs.

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