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.

[1]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[2]  D N Shapiro,et al.  Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. , 1994, Science.

[3]  A. Carbone,et al.  High incidence of monoclonal EBV episomes in Hodgkin's disease and anaplastic large‐cell ki‐1‐positive lymphomas in HIV‐1‐positive patients , 1993, International journal of cancer.

[4]  P. Chan,et al.  Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome. , 1993, DNA and cell biology.

[5]  G. Frizzera.  The distinction of Hodgkin's disease from anaplastic large cell lymphoma. , 1992, Seminars in diagnostic pathology.

[6]  N. Harris,et al.  The relationship between Hodgkin's disease and non-Hodgkin's lymphoma. , 1992, Seminars in diagnostic pathology.

[7]  J. Hainsworth,et al.  Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  Christine Chomienne,et al.  The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus , 1990, Nature.

[9]  J. Gogusev,et al.  Genotype markers and proto‐oncogene analysis in the cd30‐positive “malignant histiocytosis” del cell line with t(5;6)(q35;p21) , 1990, International journal of cancer.

[10]  M. Ladanyi,et al.  Immunohistochemical, molecular, and cytogenetic analysis of a consecutive series of 20 peripheral t‐cell lymphomas and lymphomas of uncertain lineage, including 12 Ki‐I positive lymphomas , 1990, Genes, chromosomes & cancer.

[11]  R. Larson,et al.  Morphology in Ki‐1 (CD30)‐Positive Non Hodgkin's Lymphoma Is Correlated with Clinical Features and the Presence of a Unique Chromosomal Abnormality, t(2;5)(p23;q35) , 1990, The American journal of surgical pathology.

[12]  S. Smith,et al.  The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias. , 1989, Science.

[13]  R. Warnke,et al.  Lack of involvement of the c-fms and N-myc genes by chromosomal translocation t(2;5)(p23;q35) common to malignancies with features of so-called malignant histiocytosis. , 1989, Blood.

[14]  M. Sasaki,et al.  A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis. , 1989, Blood.

[15]  C. Lehner,et al.  Major nucleolar proteins shuttle between nucleus and cytoplasm , 1989, Cell.

[16]  Qing-Rong Liu,et al.  Characterization of the cDNA encoding human nucleophosmin and studies of its role in normal and abnormal growth. , 1989, Biochemistry.

[17]  F. Berger,et al.  A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma (‘Ki‐1 lymphoma') , 1989, British journal of haematology.

[18]  P. Sherrington,et al.  A Ki-1 (CD30)-positive human cell line (Karpas 299) established from a high-grade non-Hodgkin's lymphoma, showing a 2;5 translocation and rearrangement of the T-cell receptor beta-chain gene , 1988 .

[19]  H. Stein,et al.  Genotypic analysis of large cell lymphomas which express the Ki‐1 antigen , 1987, Histopathology.

[20]  B. Woda,et al.  Childhood Ki-1 lymphoma presenting with skin lesions and peripheral lymphadenopathy. , 1986, Blood.

[21]  K. Lennert,et al.  The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. , 1985, Blood.

[22]  E. Canaani,et al.  Fused transcript of abl and bcr genes in chronic myelogenous leukaemia , 1985, Nature.

[23]  P. Nowell,et al.  Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. , 1984, Science.

[24]  H Stein,et al.  Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). , 1984, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[25]  V. Diehl,et al.  Identification of Hodgkin and sternberg‐reed cells as a unique cell type derived from a newly‐detected small‐cell population , 1982, International journal of cancer.

[26]  V. Diehl,et al.  Production of a monoclonal antibody specific for Hodgkin and Sternberg–Reed cells of Hodgkin's disease and a subset of normal lymphoid cells , 1982, Nature.

[27]  H. Stein,et al.  Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. , 1992, Cell.

[28]  S. Pileri,et al.  Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma: dissociation between phenotype and genotype. , 1989, Leukemia research.

[29]  L. G. Davis,et al.  Basic methods in molecular biology , 1986 .