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

Written2014-06Xiaoming Xing, Andrew L Feldman
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)

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 1685

Clinics and Pathology

Disease Anaplastic large cell lymphoma, ALK-positive
Phenotype / cell stem 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.
 
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
Location 9q33.2
Protein 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
Location 2p23.2
Protein 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

Hybrid gene
Description Expressed, as demonstrated by next-generation and Sanger sequencing.
  
Fusion Protein
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.
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

Novel TRAF1-ALK fusion identified by deep RNA sequencing of anaplastic large cell lymphoma.
Feldman AL, Vasmatzis G, Asmann YW, Davila J, Middha S, Eckloff BW, Johnson SH, Porcher JC, Ansell SM, Caride A.
Genes Chromosomes Cancer. 2013 Nov;52(11):1097-102. doi: 10.1002/gcc.22104. Epub 2013 Sep 2.
PMID 23999969
 

Citation

This paper should be referenced as such :
X Xing, AL Feldman
t(2;9)(p23;q33) TRAF1/ALK
Atlas Genet Cytogenet Oncol Haematol. 2015;19(2):145-147.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0209p23q33ID1685.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(2;9)(p23;q33) TRAF1/ALK

External links

arrayMap (UZH-SIB Zurich)TRAF1 (9q33.2) ALK (2p23.2)

TRAF1 (9q33.2) ALK (2p23.2)

Mitelman databaset(2;9)(p23;q33) [Case List]    t(2;9)(p23;q33) [Association List] Mitelman database (CGAP - NCBI)
arrayMap[select an item]
 
Mitelman databaseTRAF1/ALK [MCList]  TRAF1 (9q33.2) ALK (2p23.2)
Mitelman databaseTRAF1/ALK [MCList]  TRAF1 (9q33.2) ALK (2p23.2)
 
Disease databaset(2;9)(p23;q33) TRAF1/ALK
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