NEOPLASIA ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases

Expression of ALK protein by lymphoid cells and the description of variant ana-plastic lymphoma kinase (ALK) transloca-tions have typically been restricted to cases of T-cell and null anaplastic large-cell lymphoma (ALCL). All such cases result from a novel fusion created by the ALK gene on chromosome 2p23 and NPM on 5q35 or other variant translocation partners. A rare variant of diffuse large B-cell lymphoma (DLBCL), originally de-scribed in 1997, was thought to overex-press full-length ALK in contrast to a chimeric protein characteristic of ALCL. However, full-length ALK protein lacks tyrosine kinase activity and thus the mechanism of oncogenesis has remained elusive. We describe 6 cases of ALK DLBCL characterized by a simple or com-plex t(2;17)(p23;q23) involving the clath-rin gene (CLTC) at chromosome band 17q23 and the ALK gene at chromosome band 2p23. All cases were studied using fluorescence in situ hybridization (FISH), complemented in one case with standard cytogenetic analysis, multicolor karyotyp-ing (M-FISH), and reverse transcriptase– polymerase chain reaction. These results clearly demonstrate that most cases of ALK DLBCL share the same mechanism of deregulated ALK expression. More-over, these results demonstrate the pres-ence of CLTC-ALK fusions in these tu-mors and extend the list of diseases associated with this genetic abnormality to include classical T-cell or null ALCL, ALK DLBCL, and inflammatory myofibro-blastic tumors. (Blood. 2003;102:2568-2573) © 2003 by The American Society of Hematolog