PMID- 12763927 OWN - NLM STAT- MEDLINE DCOM- 20031029 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 102 IP - 7 DP - 2003 Oct 1 TI - ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases. PG - 2568-73 AB - Expression of ALK protein by lymphoid cells and the description of variant anaplastic lymphoma kinase (ALK) translocations 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 described in 1997, was thought to overexpress 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 complex t(2;17)(p23;q23) involving the clathrin 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 karyotyping (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. Moreover, these results demonstrate the presence of CLTC-ALK fusions in these tumors and extend the list of diseases associated with this genetic abnormality to include classical T-cell or null ALCL, ALK+ DLBCL, and inflammatory myofibroblastic tumors. FAU - Gascoyne, Randy D AU - Gascoyne RD AD - Department of Oncogeneiss and Signaling in Hematopoietic Cells, Instiut National de la Sante et de la Recherche Medicale U-563, Centre de Physiopatholgie de Toulouse-Purpan, France. FAU - Lamant, Laurence AU - Lamant L FAU - Martin-Subero, Jose I AU - Martin-Subero JI FAU - Lestou, Valia S AU - Lestou VS FAU - Harris, Nancy Lee AU - Harris NL FAU - Muller-Hermelink, Hans-Konrad AU - Muller-Hermelink HK FAU - Seymour, John F AU - Seymour JF FAU - Campbell, Lynda J AU - Campbell LJ FAU - Horsman, Douglas E AU - Horsman DE FAU - Auvigne, Isabelle AU - Auvigne I FAU - Espinos, Estelle AU - Espinos E FAU - Siebert, Reiner AU - Siebert R FAU - Delsol, Georges AU - Delsol G LA - eng GR - 1-U01-CA84967-01/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030522 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Clathrin) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (RNA, Messenger) RN - 0 (oncoprotein CLTCL-ALK) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Anaplastic Lymphoma Kinase MH - Clathrin/*genetics MH - Gene Expression Regulation, Neoplastic MH - Gene Rearrangement/*genetics MH - Humans MH - Immunophenotyping MH - In Situ Hybridization, Fluorescence/methods MH - Lymphoma, B-Cell/*genetics/pathology MH - Lymphoma, Large B-Cell, Diffuse/*genetics/pathology MH - Oncogene Proteins, Fusion/*genetics MH - Protein-Tyrosine Kinases/*genetics MH - RNA, Messenger/analysis MH - Receptor Protein-Tyrosine Kinases MH - Reverse Transcriptase Polymerase Chain Reaction MH - Translocation, Genetic MH - Tumor Cells, Cultured EDAT- 2003/05/24 05:00 MHDA- 2003/10/30 05:00 CRDT- 2003/05/24 05:00 PHST- 2003/05/24 05:00 [pubmed] PHST- 2003/10/30 05:00 [medline] PHST- 2003/05/24 05:00 [entrez] AID - S0006-4971(20)44089-3 [pii] AID - 10.1182/blood-2003-03-0786 [doi] PST - ppublish SO - Blood. 2003 Oct 1;102(7):2568-73. doi: 10.1182/blood-2003-03-0786. Epub 2003 May 22.