Analysis of the t(2;5) (p23;q35) translocation in CD30+ primary cutaneous lymphoproliferative disorders and Hodgkin's disease.
The t(2;5) (p23;q35) chromosomal translocation is found in about 40% of lymph node-based CD30+ anaplastic large cell lymphomas of T-cell or null-cell lineage. This translocation results in the expression of a fusion protein containing the catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the promoter for nucleophosmin (NPM), a nucleolar phosphoprotein. Expression of ALK activity, normally absent in lymphocytes, is postulated to be involved in the pathogenesis of lymphomas bearing the t(2;5) translocation. Certain primary cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to contain CD30+ large lymphoid cells. In order to determine the role of the t(2;5) translocation in these diseases, several investigators have employed a variety of techniques including cytogenetics, genomic Southern blot analysis, RNA- and DNA-based PCR assays, various forms of in-situ hybridization, and immunostaining for the p80 fusion protein encoded by the chimeric t(2;5) transcripts. These studies included approximately 415 cases of Hodgkin's disease, 65 cases of CD30+ primary cutaneous large cell lymphoma, and 38 cases of lymphomatoid papulosis. The aggregate results of these studies indicate that the t(2;5) translocation or other somatic mutations resulting in inappropriate expression of ALK are involved rarely if at all in the pathogenesis of Hodgkin's disease, but may be present in about 10% of cases of lymphomatoid papulosis and 20% of cases of CD30+ primary cutaneous large cell lymphoma. However, the t(2;5) has not been detected yet in any case involving multiple or secondary CD30+ lymphoproliferative disorders, thereby providing no evidence for a role in tumor clone progression. Additional studies will be needed to determine if t(2;5) status has any clinical significance for patients with CD30+ primary cutaneous lymphoproliferative disorders.
Wood
G S
GS
Department of Dermatology, Case Western Reserve University, and the VA Medical Center, Cleveland, Ohio 44106, USA.
D000077548:Anaplastic Lymphoma Kinase; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis*; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology; D014178:Translocation, Genetic
D017730:Ki-1 Antigen; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases