ANALYSIS OF THE T(2-5)(P23-Q35) TRANSLOCATION BY REVERSE TRANSCRIPTION-POLYMERASE CHAIN-REACTION IN CD30(-CELL LYMPHOMAS, IN OTHER NON-HODGKINS-LYMPHOMAS OF T-CELL PHENOTYPE, AND IN HODGKINS-DISEASE() ANAPLASTIC LARGE)

The t(2;5)(p23;q35) translocation is associated with a high percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell phenotyp e, This translocation was recently cloned and results in the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to a novel tyrosine k inase-encoding gene designated anaplastic lymphoma kinase (ALK) on chr omosome 2q23. Using a sensitive and specific reverse transcription-pol ymerase chain reaction (RT-PCR) assay to detect the NPM/ALK fusion tra nscript, we assessed the involvement of NPM/ALK in a series of histolo gically and immunohistochemically confirmed ALCL, in non-ALCL aggressi ve non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disea se (HD) to better define the morphologic spectrum of disease associate d with this translocation. Twenty-four cases of ALCL were selected on the basis of CD30 positivity and histologic features. Seventeen cases presented as classical nodal and extranodal disease, four cases presen ted as primary cutaneous disease, and three were associated with human immunodeficiency virus (HIV) infection. As ALCL may show overlapping histology with both HD and other aggressive non-Hodgkin's lymphomas, p articularly of T-cell phenotype (T-NHL), we also studied 34 cases of H D and 19 of T-NHL. NPM/ALK chimeric transcripts of identical size were detected in 11 of the 24 (46%) cases of ALCL. NPM/ALK fusion transcri pts were found in 11 of 17 (65%) classical ALCL cases but were not det ected in the four primary cutaneous cases of ALCL or in the three HIV- related ALCL cases. In addition, NPM/ALK transcripts were not detected in any of the 34 cases of HD or in the 19 cases of T-NHL. These data indicate that NPM/ALK fusion transcripts occur in a high percentage of classical nodal ALCL (65%). In addition, these data strongly suggest that ALCL, as defined in this study, is not pathogenetically related t o either HD disease or the majority of other types of aggressive T-NHL .