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.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Karrman
Kristina
K
Department of Clinical Genetics, University Hospital, Lund, Sweden. Kristina.Karrman@med.lu.se
Andersson
Anna
A
Björgvinsdóttir
Helga
H
Strömbeck
Bodil
B
Lassen
Carin
C
Olofsson
Tor
T
Nguyen-Khac
Florence
F
Berger
Roland
R
Bernard
Olivier
O
Fioretos
Thoas
T
Johansson
Bertil
B
D000293:Adolescent; D002881:Chromosomes, Human, Pair 12; D002883:Chromosomes, Human, Pair 14; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000089703:Fibroblast Growth Factor-23; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; C000717427:FGF23 protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000089703:Fibroblast Growth Factor-23