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ETV6-NTRK3 Gene Fusions and Trisomy 11 Establish a Histogenetic Link between Mesoblastic Nephroma and Congenital Fibrosarcoma¹

Department of Pathology, British Columbia's Children's Hospital, Vancouver, British Columbia, V6H 3V4 Canada [S. R. K., M. J. G., P. H. B. S.]; Department of Pathology, Primary Children's Medical Center, Salt Lake City, Utah 84113-1100 [T. J. P.]; Division of Pediatric Pathology, Loma Linda University, Loma Linda, California 92350 [J. B. B.]; and Department of Pediatrics, Cross Cancer Institute, and Departments of Pediatrics and Oncology, University of Alberta, Edmonton, Alberta, T6G 1Z2 Canada [P. E. G.]

Congenital mesoblastic nephroma (CMN) is an infantile spindle cell tumor of the kidney that is subdivided into "classical" and "cellular" forms based on the degree of cellularity and mitotic activity. The histogenesis of CMN remains obscure, but relationships to other pediatric renal neoplasms have been proposed. However, cellular CMN is virtually identical histologically to congenital fibrosarcoma (CFS), a malignant tumor of fibroblasts in children of the same age group. Moreover, cytogenetic studies have reported common trisomies in CFS and cellular CMN, particularly of chromosome 11. We show here that t(12;15)(p13;q25)-associated ETV6-NTRK3 gene fusions described in CFS are also present 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 four classical CMNs tested were negative, as were cases of Wilms' tumor and clear cell sarcoma of the kidney. Moreover, we found trisomy 11 only in cellular or mixed CMNs with the ETV6-NTRK3 gene fusion. Our studies indicate that classical and cellular CMN have different genetic features and support the concept that cellular CMN is histogenetically related to CFS. They also provide insight into potential mechanisms involved in the transformation of the classical into the cellular form of CMN.

¹ Supported by a Grant from the National Cancer Institute of Canada with funds from the Terry Fox Run (to P. H. B. S.) and by National Wilms' Tumor Study Group Grant USPHS 42326.

² To whom requests for reprints should be addressed, at Department of Pathology, British Columbia's Children's Hospital, Room L200, 4480 Oak Street, Vancouver, British Columbia, V6H 3V4 Canada.

Received 7/28/98. Accepted 9/29/98.

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