CONGENITAL MESOBLASTIC NEPHROMA T(12-15) IS ASSOCIATED WITH ETV6-NTRK3 GENE FUSION - CYTOGENETIC AND MOLECULAR RELATIONSHIP TO CONGENITAL (INFANTILE) FIBROSARCOMA

Morphological, cytogenetic, and biological evidence supports a relatio nship between congenital (infantile) fibrosarcoma (CFS) and congenital mesoblastic nephroma (CMN). These tumors have a very similar histolog ical appearance, and they are both associated with polysomies for chro mosomes 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 mesoblasti c 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 transcriptas e polymerase chain reaction acid sequence analysis, 2) genomic ETV6-re gion 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-reg ion rearrangement in five of six CMNs and in five of five CFSs, The ET V6-NTRK3 fusion transcripts and/or ETV-region chromosome rearrangement s were demonstrated in two CMNs and one CFS that lacked chromosome pol ysomies. These findings demonstrate that t(12;15) translocation, and t he associated ETV6-NTRK3 fusion, can antedate acquisition of chromosom e polysomies in CMN and CFS, CMN and CFS are pathogenetically related, and it is likely that they represent a single neoplastic entity, aris ing in either renal or soft tissue locations.