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Jefferson Cancer Institute, Department of Microbiology and Immunology, Philadelphia, Pennsylvania 19107 [F. B., C. M. C.]; Departments of Experimental Oncology and Hematology Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101 and Department of Pediatrics, University of Tennessee College of Medicine, Memphis, Tennessee 38163 [S. W. M.]; Institute of Pathology, Klinikum Steglitz, Free University of Berlin, Germany [M. H., H. S.]; and Institute of Hematology, University of Bologna, Bologna, Italy [S. P.]
The (2;5)(p23;q35) translocation which results in the fusion of the NPM (nucleophosmin) gene on chromosome 5q35 with the novel ALK (anaplastic lymphoma kinase) gene on chromosome 2p23 [S.W. Morris et al., Science (Washington DC), 263: 1281–1284, 1994] is associated with Ki-1 (CD30)-positive anaplastic large cell lymphomas (ALCL); a group of morphologically and immunophenotypically heterogeneous high grade large cell lymphomas (LCL), which share many characteristics with Hodgkin's disease (HD), including the presence of variable numbers of Reed-Sternberg-like cells and the expression of CD30 antigen.
Using a DNA probe immediately 5' to the NPM coding sequences, we have examined NPM gene rearrangements by Southern blotting in 5 Ki-1-positive lymphoma cell lines carrying a translocation involving the 5q35 breakpoint and in 25 Ki-positive lymphoma tumors, including 9 HD. Using this method, we detected rearrangements in all cell lines with apparent clustering of the breakpoints. Analysis of 25 Ki-1-positive lymphomas indicated that only 4 neoplasms, including two HD, had NPM gene rearrangements. Thus, our findings suggest that only a subset of ALCL has detectable involvement of the NPM gene. In addition, the presence of NPM gene rearrangements in HD indicates the involvement of this gene in a fraction of HD. Thus, NPM gene rearrangements may identify a certain subtype in ALCL and HD which may be closely related.
1 This work was supported by National Cancer Institute Grants CA 39860 (to C. M. C.), K08 CA 01702 (to S. W. M.), the Research Fellowship Award 5 F31 CA60352-02 (to F. B.), and the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital.
2 To whom requests for reprints should be addressed, at Department of Microbiology and Immunology, Jefferson Cancer Institute, 233 S. 10th Street, Philadelphia, PA 19107.
Received 3/23/94. Accepted 4/21/94.
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