title: Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease.
abstract: The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.
authors.affiliation: Department of Pathology, New York University Medical Center, New York, USA.
authors.forename: H T
authors.initials: HT
authors.lastname: Yee
authors.forename: M
authors.initials: M
authors.lastname: Ponzoni
authors.forename: A
authors.initials: A
authors.lastname: Merson
authors.forename: M
authors.initials: M
authors.lastname: Goldstein
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
authors.forename: M
authors.initials: M
authors.lastname: Chilosi
authors.forename: F
authors.initials: F
authors.lastname: Menestrina
authors.forename: S
authors.initials: S
authors.lastname: Pittaluga
authors.forename: C
authors.initials: C
authors.lastname: de Wolf-Peeters
authors.forename: M
authors.initials: M
authors.lastname: Shiota
authors.forename: S
authors.initials: S
authors.lastname: Mori
authors.forename: G
authors.initials: G
authors.lastname: Frizzera
authors.forename: G
authors.initials: G
authors.lastname: Inghirami
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D015139:Blotting, Southern; D002889:Chromosomes, Human, Pair 2 / Q000648:ultrastructure*; D002895:Chromosomes, Human, Pair 5 / Q000648:ultrastructure*; D004273:DNA, Neoplasm / Q000032:analysis; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008215:Lymphocytes, Null / Q000378:metabolism / Q000473:pathology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D056489:Nucleoplasmins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D056489:Nucleoplasmins; D015514:Oncogene Proteins, Fusion; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases