Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas.
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 heterogenous 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.
Bullrich
F
F
Jefferson Cancer Institute, Department of Microbiology and Immunology, Philadelphia, Pennsylvania 19107.
Morris
S W
SW
Hummel
M
M
Pileri
S
S
Stein
H
H
Croce
C M
CM
D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D000090243:Nucleophosmin; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin