Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma

Am J Pathol. 1998 Nov;153(5):1451-8. doi: 10.1016/S0002-9440(10)65732-X.


Morphological, cytogenetic, and biological evidence supports a relationship between congenital (infantile) fibrosarcoma (CFS) and congenital mesoblastic nephroma (CMN). These tumors have a very similar histological appearance, and they are both associated with polysomies for chromosomes 8, 11, 17, and 20. Recently, CFS was shown to contain a novel t(12; 15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion. The aims of this study were to determine whether congenital mesoblastic nephroma contains the t(12;15)(p13;q25) translocation and ETV6-NTRK3 gene fusion and whether ETV6-NTRK3 fusions, in CMN and CFS, antedate acquisition of nonrandom chromosome polysomies. To address these aims, we evaluated 1) ETV6-NTRK3 fusion transcripts by reverse transcriptase polymerase chain reaction and sequence analysis, 2) genomic ETV6-region chromosomal rearrangement by fluorescence in situ hybridization, and 3) chromosomal polysomies by karyotyping and fluorescence in situ hybridization. We report ETV6-NTRK3 fusion transcripts and/or ETV6-region rearrangement in five of six CMNs and in five of five CFSs. The ETV6-NTRK3 fusion transcripts and/or ETV-region chromosome rearrangements were demonstrated in two CMNs and one CFS that lacked chromosome polysomies. These findings demonstrate that t(12;15) translocation, and the associated ETV6-NTRK3 fusion, can antedate acquisition of chromosome polysomies in CMN and CFS. CMN and CFS are pathogenetically related, and it is likely that they represent a single neoplastic entity, arising in either renal or soft tissue locations.

MeSH terms

  • Artificial Gene Fusion*
  • Chromosomes, Human, Pair 12*
  • Chromosomes, Human, Pair 15*
  • DNA-Binding Proteins / genetics*
  • ETS Translocation Variant 6 Protein
  • Female
  • Fibrosarcoma / congenital*
  • Fibrosarcoma / genetics*
  • Genetic Markers
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Karyotyping
  • Kidney Neoplasms / genetics*
  • Male
  • Nephroma, Mesoblastic / genetics*
  • Proto-Oncogene Proteins c-ets
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, trkC
  • Receptors, Nerve Growth Factor / genetics*
  • Repressor Proteins*
  • Soft Tissue Neoplasms / congenital*
  • Soft Tissue Neoplasms / genetics*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Genetic Markers
  • Proto-Oncogene Proteins c-ets
  • Receptors, Nerve Growth Factor
  • Repressor Proteins
  • Transcription Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkC