title: Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma.
abstract: 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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Rubin
authors.forename: C J
authors.initials: CJ
authors.lastname: Chen
authors.forename: T W
authors.initials: TW
authors.lastname: Morgan
authors.forename: S
authors.initials: S
authors.lastname: Xiao
authors.forename: H E
authors.initials: HE
authors.lastname: Grier
authors.forename: H P
authors.initials: HP
authors.lastname: Kozakewich
authors.forename: A R
authors.initials: AR
authors.lastname: Perez-Atayde
authors.forename: J A
authors.initials: JA
authors.lastname: Fletcher
mesh_terms: D019677:Artificial Gene Fusion; D002881:Chromosomes, Human, Pair 12; D002884:Chromosomes, Human, Pair 15; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005354:Fibrosarcoma / Q000151:congenital* / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D018201:Nephroma, Mesoblastic / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D012097:Repressor Proteins; D012983:Soft Tissue Neoplasms / Q000151:congenital* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D005819:Genetic Markers; D050783:Proto-Oncogene Proteins c-ets; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein