TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations

Anaplastic large cell lymphoma (ALCL) is associated with the t(2;5)(p23;q35 ), which generates the NPM-ALK fusion gene encoding an 80-kD protein. Sever al studies have suggested that genes other than NPM may be fused to the ALK gene. Here we have identified TRK-fused gene (TFG) as a new ALK partner in 2 ALCL, 1 of which exhibited a t(2;3)(p23;q21). In these cases, TFG was in volved in 2 different fusion genes, TFG-ALK(S) and TFG-ALK(L), coding respe ctively 85-kD and 97-kD chimeric proteins. The ALK breakpoint in these tran slocations was the same as in the classic t(2;5) translocation, These 2 pro teins were both active in an in vitro tyrosine kinase assay showing that th e new cloned cDNA sequences are translated into chimeric proteins with func tional activity. These findings indicate that TFG can provide an alternativ e to NPM as a fusion partner responsible for activation of the ALK and the pathogenesis of ALCL. (C) 1999 by The American Society of Hematology.