t(2;9)(p23;q33) TRAF1/ALK

2014-06-01   Xiaoming Xing , Andrew L Feldman 

1.Department of Pathology, Affiliated Hospital of Medical College, Qingdao University, 16 Jiangsu Road, Qingdao, China (XX); Department of Laboratory Medicine, Pathology, College Of Medicine, Mayo Clinic, 200 First Street SW, Hilton Building, Room 8-00F, Rochester, MN 55905 USA (ALF)

Clinics and Pathology

Disease

Phenotype stem cell origin

Mature (peripheral) T cell.

Etiology

No etiologic factors are known.

Epidemiology

The single reported case occurred in an adult male (Feldman et al., 2013).

Clinics

Presentation in the single reported case was with lymphadenopathy and rash.

Pathology

The pathologic findings in the single reported case were typical for the so-called "lymphohistiocytic pattern" previously reported in ALK-positive ALCLs.
Atlas Image
ALCL, ALK-positive, with t(2;9)(p23;q33) TRAF1/ALK. H&E stain of paraffin embedded tumor tissue shows large atypical cells with cytologic features of "hallmark" cells characteristic of ALCL. Immunohistochemical staining for CD30 shows strong positivity in the tumor cells, with a membranous and Golgi zone distribution. Staining for ALK shows strong cytoplasmic positivity without nuclear staining. The absence of nuclear staining is characteristic for an alternate (non-NPM1) ALK fusion partner. TRAF1 was identified as the partner gene by RNA sequencing.

Treatment

The patient in the reported case was treated with anthracycline-based multi-agent chemotherapy.

Prognosis

Among peripheral T-cell lymphomas, ALK-positive ALCLs tend to have favorable outcomes. The patient in the reported case had a recurrence requiring additional therapy, but was alive without evidence of disease at last follow-up, 28 years after diagnosis.

Cytogenetics

Note

Deep RNA sequencing of tumor tissue identified a chimeric transcript fusing the end of exon 6 of TRAF1 to the start of exon 20 of ALK. The TRAF1-ALK fusion transcript was confirmed at the mRNA level by Sanger sequencing and the encoded fusion protein was visualized by Western blot.

Cytogenetics morphological

Karyotypic findings have not been reported.

Additional anomalies

Unknown.

Variants

Unknown.

Genes Involved and Proteins

Gene name
TRAF1 (TNF receptor associated factor 1)
Location
9q33.2
Protein description
TRAF1 encodes the TRAF1 protein, a member of the tumor necrosis factor receptor-associated factor family of signaling proteins. TRAF1 associates with, and mediates signal transduction from, various receptors of the TNFR superfamily. TRAF1 and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB.
Gene name
ALK (anaplastic lymphoma receptor tyrosine kinase)
Location
2p23.2
Protein description
ALK encodes a receptor tyrosine kinase, the anaplastic lymphoma kinase (ALK), which belongs to the insulin receptor superfamily and is critical in the development of the brain. ALK fusion proteins are critical in the pathogenesis of ALK-positive ALCLs and a variety of other hematopoietic and non-hematopoietic neoplasms, in which they serve both as a diagnostic biomarker and potential therapeutic target.

Result of the Chromosomal Anomaly

Description

Expressed, as demonstrated by next-generation and Sanger sequencing.

Note

The TRAF1-ALK fusion transcript and TRAF1-ALK fusion protein both were expressed in the reported case. The function of the fusion has not been reported.

Description

Expressed, as demonstrated by Western blot and immunohistochemistry.

Bibliography

Pubmed IDLast YearTitleAuthors
239999692013Novel TRAF1-ALK fusion identified by deep RNA sequencing of anaplastic large cell lymphoma.Feldman AL et al

Summary

Fusion gene

TRAF1/ALK TRAF1 (9q33.2) ALK (2p23.2) M|TRAF1/ALK TRAF1 (9q33.2) ALK (2p23.2) M t(2;9)(p23;q33)

Citation

Xiaoming Xing ; Andrew L Feldman

t(2;9)(p23;q33) TRAF1/ALK

Atlas Genet Cytogenet Oncol Haematol. 2014-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1685/t(2;9)(p23;q33)

External Links