t(7;12)(q34;p13) TRB/CCND2
t(12;14)(p13;q11) TRA or TRD/CCND2

2006-06-01   Emmanuelle Clappier , Jean Soulier 

1.Laboratoire central dHématologie et U728 INSERM Institut Universitaire dHématologie Hopital Saint-Louis et Université Paris 7 1, AV Claude Vellefaux 75010 Paris, France
2.Laboratoire central d Hématologie et U728 INSERM Institut Universitaire d Hématologie Hopital Saint-Louis et Université Paris 7 1, AV Claude Vellefaux 75010 Paris, France

Clinics and Pathology

Phenotype stem cell origin

T cell precursor. These translocations are not restricted to a single maturation stage.

Epidemiology

less than 5% among T-ALL.

Cytology

Lymphoblasts

Cytogenetics

Atlas Image
Example of FISH performed on bone marrow metaphase from a patient with t(7;12)(q34;p13). Dual color FISH using whole chromosome paint for chromosome 7 (green) and chromosome 12 (red) showed the reciprocal translocation.

Cytogenetics morphological

t(7;12)(q34;p13) may be barely detectable by chromosome banding techniques alone.

Cytogenetics molecular

Rearrangement of the CCND2 locus at 12p13.3 may be detected by dual color FISH using CCND2 flanking probes.
Atlas Image
Example of double colour FISH performed on bone marrow interphasic nuclei from a patient with t(7;12)(q34;p13) using CCND2 flanking probes at 12p13. The centromeric BAC clone RP11-388F6 (red) and the telomeric BAC clone RP11-320N7 (green) show one fusion signal at the normal chromosome 12, and dissociated signals at der(12) (red signal) and der(7) (green signal).

Genes Involved and Proteins

Note
The t(7;12)(q34;p13) translocation has not to be confused with the t(7;12)(q36;p13) involving ETV6 at 12p13.1 and HLXB9 at 7q36, which is found in infant myeloid leukemias.
Gene name
CCND2 (cyclin D2)
Location
12p13.32
Dna rna description
5 exons, 2.1 kb mRNA, 5-3 telomere to centromere orientation.
Protein description
Cyclin D2; 289 amino acids; 33 kDa. Cyclin D2 is a regulator of the progression through G1-phase and G1 to S-phase transition of the cell cycle.
Gene name
TRA (T cell Receptor Alpha)
Location
14q11.2
Protein description
T-cell receptor alpha
Gene name
TRD (T cell Receptor Delta)
Location
14q11.2
Protein description
T-cell receptor delta
Gene name
TRB (T cell Receptor Beta)
Location
7q34
Protein description
T-cell receptor beta

Result of the Chromosomal Anomaly

Note

No fusion protein

Description

t(7;12)(q34;p13) and t(12;14)(p13;q11) translocations result in juxtaposition of TRA/D or TRB regulatory sequences to the CCND2 gene, leading to deregulated expression of the CCND2 gene.

Note

T-ALL cases with t(7;12)(q34;p13) or t(12;14)(p13;q11) can be associated to other oncogenic abnormalities, such as overexpression of the oncogenes TAL1, TLX3/HOX11L2, or HOXA genes, activating NOTCH1 mutations, and/or CDKN2A/p16/ARF locus deletion.

Oncogenesis

CCND2 gene expression is tightly regulated throughout thymocyte differenciation. Its deregulated expression in T-ALL cases with t(7;12)(q34;p13) or t(12;14)(p13;q34) is likely to play a role in T-cell oncogenesis.

Bibliography

Pubmed IDLast YearTitleAuthors
162700382006Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T-cell acute lymphoblastic leukemias.Clappier E et al
165489142006Deregulation 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.Karrman K et al
92643921997A new breakpoint, telomeric to TEL/ETV6, on the short arm of chromosome 12 in T cell acute lymphoblastic leukemia.Le Coniat M et al

Summary

Fusion gene

TRB/CCND2 TRB (-) CCND2 (12p13.32) M t(7;12)(q34;p13)

Note

The 2 translocations are variants of each other, and probably share the same biological significance
Atlas Image
R-band analysis. Partial karyotypes showing t(7;12)(q34;p13) (left panel), and t(12;14)(p13;q11) (right panel)

Citation

Emmanuelle Clappier ; Jean Soulier

t(7;12)(q34;p13) TRB/CCND2
t(12;14)(p13;q11) TRA or TRD/CCND2

Atlas Genet Cytogenet Oncol Haematol. 2006-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1434/t(7;12)(q34;p13)

External Links