ETV6-NTRK3 GENE FUSIONS AND TRISOMY-11 ESTABLISH A HISTOGENETIC LINK BETWEEN MESOBLASTIC NEPHROMA AND CONGENITAL FIBROSARCOMA

Congenital mesoblastic nephroma (CMN) is an infantile spindle cell tum or of the kidney that is subdivided into ''classical'' and ''cellular' ' forms based on the degree of cellularity and mitotic activity. The h istogenesis of CMN remains obscure, but relationships to other pediatr ic renal neoplasms have been proposed. However, cellular CMN is virtua lly identical histologically to congenital fibrosarcoma (CFS), a malig nant tumor of fibroblasts in children of the same age group. Moreover, cytogenetic studies have reported common trisomies in CFS and cellula r CMN, particularly of chromosome 11. We show here that t(12;15)(p13;q 25)-associated ETV6-NTRK3 gene fusions described in CFS are also prese nt in cellular CMN. ETV6-NTRK3 chimeric transcripts were detected in 8 of 9 cellular CMNs and 2 of 2 mixed CMNs. In contrast, all of the fou r classical CMNs tested were negative, as were cases of Wilms' tumor a nd clear cell sarcoma of the kidney. Moreover, we found trisomy 11 onl y in cellular or mixed CMNs with the ETV6-NTRK3 gene fusion. Our studi es indicate that classical and cellular CMN have different genetic fea tures and support the concept that cellular CMN is histogenetically re lated to CFS. They also provide insight into potential mechanisms invo lved in the transformation of the classical into the cellular form of CMN.