t(6;14)(p25.3;q11.2) TRA/IRF4

2013-03-01   Andrew L Feldman 

1.Department of Laboratory Medicine, Pathology, College Of Medicine, Mayo Clinic, 200 First Street SW, Hilton Building, Room 11-52D, Rochester, MN 55905 USA

Clinics and Pathology

Phenotype stem cell origin

Mature (peripheral) cytotoxic alpha-beta T-cell origin.

Etiology

No etiologic factors are known.

Epidemiology

Adult males (age range, 67-82 years).

Clinics

Presentation with cytopenias in the absence of lymphadenopathy, sometimes with skin involvement.

Pathology

The bone marrow is hypercellular with the normal marrow elements replaced by an extensive infiltrate of atypical, mostly medium-sized lymphoid cells with irregular nuclear outlines. Admixed plasma cells and a background of reticulin fibrosis are present. The tumor cells display an abnormal T-cell phenotype with expression of CD3, the cytotoxic marker TIA1 (+/- granzyme B), and T-cell receptor-beta (beta-F1), but without coexpression of CD5. Most cases express CD4 and lack expression of CD25 and CD30. IRF4/MUM1 protein is expressed in tumor cell nuclei. Cases tested for EBV by in situ hybridization have been negative.
Atlas Image
(A) Atypical lymphocytes in bone marrow smear from patient with PTCL, NOS with t(6;14)(p25.3;q11.2) (Wright-Giemsa, original magnification x1000). (B) Bone marrow trephine biopsy (H&E, x400). Tumor cells are (C) positive for CD2, (D) negative for CD5, (E) positive for granzyme B, and (F) positive for nuclear IRF4/MUM1 (x400).

Treatment

No treatment data are available.

Prognosis

The prognosis has not been established.

Cytogenetics

Atlas Image
t(6;14)(p25.3;q11.2) [G-banding].

Cytogenetics morphological

The rearrangement can be detected in standard G-banded karyotype.

Cytogenetics molecular

The rearrangement can be detected using dual-fusion fluorescence in situ hybridization with probes to the IRF4 and TCR@ loci.

Genes Involved and Proteins

Note
The IRF4/MUM1 protein is expressed in cases with t(6;14)(p25.3;q11.2). This expression likely results from the translocation, but this has not been proved.
Gene name
IRF4 (interferon regulatory factor 4)
Location
6p25.3
Dna rna description
Nine-exon gene on 6p25.3.
Protein description
The gene encodes interferon regulatory factor-4 (IRF4)/multiple myeloma oncogene-1 (MUM1), a transcription factor in the IRF family. Its expression limited mainly to lymphocytes and is critical in lymphocyte activation.
Gene name
TRA (T cell Receptor Alpha)
Location
14q11.2
Note
Other name: TRA@.
Dna rna description
~ 1Mb on 14q11.2 containing TCR alpha V, J, and C regions, as well as the TCR-delta locus.
Protein description
TRA@ encodes the T-cell receptor-alpha chains, translated from transcripts resulting from rearrangement of the TRAV and TRAJ regions and from TRAC.

Result of the Chromosomal Anomaly

Note

No RNA studies have been reported on cases with t(6;14)(p25.3;q11.2). Most translocations involving TRA@ in T-cell neoplasia do not produce fusion transcripts.No studies of potential fusion proteins have been reported on cases with t(6;14)(p25.3;q11.2). Most translocations involving TRA@ in T-cell neoplasia do not produce fusion proteins.

Bibliography

Pubmed IDLast YearTitleAuthors
189876572009Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas.Feldman AL et al
193838292009IRF4: Immunity. Malignancy! Therapy?Shaffer AL et al

Summary

Fusion gene

TRA/IRF4 TRA (-) IRF4 (6p25.3) M t(6;14)(p25;q11)

Citation

Andrew L Feldman

t(6;14)(p25.3;q11.2) TRA/IRF4

Atlas Genet Cytogenet Oncol Haematol. 2013-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1606/t(6;14)(p25-3;q11-2)

External Links