RBM10-TFE3 renal cell carcinoma. A Potential diagnostic pitfall due to cryptic intrachromosomal Xp11.2 inversion resulting in false-negative TFE3 FISH Academic Article uri icon


MeSH Major

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell
  • Chromosome Inversion
  • Chromosomes, Human, X
  • Gene Fusion
  • In Situ Hybridization, Fluorescence
  • Kidney Neoplasms
  • RNA-Binding Proteins


  • Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion. TFE3 rearrangement was not detected by conventional TFE3 break-apart FISH, but was suggested by strong diffuse TFE3 immunoreactivity in a clean background. We then developed novel fosmid probes to detect the RBM10-TFE3 gene fusion in archival material. These cases validate RBM10-TFE3 as a recurrent gene fusion in Xp11 translocation RCC, illustrate a source of false-negative TFE3 break-apart FISH, and highlight the complementary role of TFE3 IHC and TFE3 FISH.

publication date

  • January 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5391276

Digital Object Identifier (DOI)

  • 10.1097/PAS.0000000000000835

PubMed ID

  • 28296677

Additional Document Info

start page

  • 655

end page

  • 662


  • 41


  • 5