PMID- 16548914 OWN - NLM STAT- MEDLINE DCOM- 20060824 LR - 20211203 IS - 0902-4441 (Print) IS - 0902-4441 (Linking) VI - 77 IP - 1 DP - 2006 Jul TI - Deregulation of cyclin D2 by juxtaposition with T-cell receptor alpha/delta locus in t(12;14)(p13;q11)-positive childhood T-cell acute lymphoblastic leukemia. PG - 27-34 AB - OBJECTIVES: The t(12;14)(p13;q11)--a recurrent translocation in childhood T-cell acute lymphoblastic leukemia (T-ALL)--has very recently been molecularly characterized in one case, which displayed overexpression of the cyclin D2 gene (CCND2). PATIENTS AND METHODS: We have characterized two pediatric t(12;14)-positive T-ALLs using fluorescence in situ hybridization (FISH), cDNA microarray, and real-time polymerase chain reaction (PCR). RESULTS: FISH revealed breakpoints (BPs) in the T-cell receptor alpha/delta locus (14q11) and in the vicinity of the CCND2 gene at 12p13. To investigate the expression of genes in 12p13, cDNA microarray analysis was performed. Expression data for eight genes, including CCND2, surrounding the 12p BP were compared with those in other T-ALLs. The t(12;14)-positive T-ALL displayed an increased expression of CCND2 compared to the controls, whereas the expression of the other genes was similar in all T-ALLs. Expression of CCND2 and two additional genes (PARP11 and FGF23), close to the 12p BP, was investigated with real-time PCR of the two t(12;14)-positive cases and four controls. Neither PARP11 nor FGF23 displayed expression differences among the T-ALLs, whereas CCND2 was clearly overexpressed in both t(12;14)-positive cases as compared to the mean expression level in the controls. CONCLUSION: We have confirmed, in two additional cases, that the recurrent T-ALL-associated t(12;14) results in overexpression of cyclin D2. The t(12;14) is the first neoplasia-associated translocation shown to result in overexpression of cyclin D2. Furthermore, it is the first example of a T-cell neoplasm with a targeted deregulation of a member of a cyclin-encoding gene family. FAU - Karrman, Kristina AU - Karrman K AD - Department of Clinical Genetics, University Hospital, Lund, Sweden. Kristina.Karrman@med.lu.se FAU - Andersson, Anna AU - Andersson A FAU - Bjorgvinsdottir, Helga AU - Bjorgvinsdottir H FAU - Strombeck, Bodil AU - Strombeck B FAU - Lassen, Carin AU - Lassen C FAU - Olofsson, Tor AU - Olofsson T FAU - Nguyen-Khac, Florence AU - Nguyen-Khac F FAU - Berger, Roland AU - Berger R FAU - Bernard, Olivier AU - Bernard O FAU - Fioretos, Thoas AU - Fioretos T FAU - Johansson, Bertil AU - Johansson B LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060317 PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (CCND2 protein, human) RN - 0 (Cyclin D2) RN - 0 (Cyclins) RN - 0 (FGF23 protein, human) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) RN - 0 (Receptors, Antigen, T-Cell, gamma-delta) RN - 7Q7P4S7RRE (Fibroblast Growth Factor-23) SB - IM MH - Adolescent MH - Chromosomes, Human, Pair 12 MH - Chromosomes, Human, Pair 14 MH - Cyclin D2 MH - Cyclins/*genetics/metabolism MH - Female MH - Fibroblast Growth Factor-23 MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Infant MH - Male MH - Polymerase Chain Reaction MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics MH - Receptors, Antigen, T-Cell, alpha-beta/*genetics/metabolism MH - Receptors, Antigen, T-Cell, gamma-delta/*genetics/metabolism MH - *Translocation, Genetic EDAT- 2006/03/22 09:00 MHDA- 2006/08/25 09:00 CRDT- 2006/03/22 09:00 PHST- 2006/03/22 09:00 [pubmed] PHST- 2006/08/25 09:00 [medline] PHST- 2006/03/22 09:00 [entrez] AID - EJH651 [pii] AID - 10.1111/j.0902-4441.2006.t01-1-EJH2553.x [doi] PST - ppublish SO - Eur J Haematol. 2006 Jul;77(1):27-34. doi: 10.1111/j.0902-4441.2006.t01-1-EJH2553.x. Epub 2006 Mar 17.