Soft Tissues: Angiomatoid fibrous histiocytoma with t(2;22)(q34;q12) EWSR1/CREB1

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Written2009-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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1. Identity

ICD-Topo C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 8836/1 Angiomatoid fibrous histiocytoma
Atlas_Id 5670
Phylum Soft Tissues::Angiomatoid fibrous histiocytoma
WHO/OMS Classification Soft Tissues

2. Clinics and Pathology

Disease Angiomatoid fibrous histiocytoma is a rare soft-tissue tumour of low metastatic potential (local recurrence below 15% of cases, and metastases occur in less than 2% of patients), often located in the extremities; it is mostly found in children and young adults. Surgical excision is the treatment of choice.
Epidemiology Twenty two cases of angiomatoid fibrous histiocytoma with a (2;22)(q34;q12) have so far been described; there were 13 male and 9 female patients, aged 16 years (median, range 3-38) (Antonescu et al., 2007; Rossi et al., 2007; Shao et al., 2009).
Pathology Cases presented either a spindle or a mixed spindle and small cell morphology; there was no case of pure small cell morphology; one case showed pleomorphism; however, the prognosis in this later case has been as good as that of other cases.

3. Cytogenetics

The t(2;22)(q34;q12) appears to be the most frequent anomaly in angiomatoid fibrous histiocytoma, while the t(12;22)(q13;q12) (5' EWSR1 - 3' ATF1), and the t(12;16)(q13;p11) (5' FUS- 3' ATF1) are rarer.

4. Genes involved and Proteins

Gene NameCREB1 (cAMP responsive element binding protein 1)
Location 2q33.3
Protein Contains a KID domain (kinase inductible domain), a basic motif (DNA binding) and a leucine-zipper for dimerization, like ATF1. Stimulates transcription by binding the cAMP response element TGACGTCA (CRE). Transcription factor.

Gene NameEWSR1 (Ewing sarcoma breakpoint region 1)
Location 22q12.2
Protein From N-term to C-term: a transactivation domain (TAD) containing multiple degenerate hexapeptide repeats, 3 arginine/glycine rich domains (RGG regions), a RNA recognition motif, and a RanBP2 type Zinc finger. Role in transcriptional regulation for specific genes and in mRNA splicing.

5. Result of the chromosomal anomaly

Hybrid Gene
Description 5' EWSR1 - 3' CREB1. EWSR1 exon 7 is fused in frame to CREB1 exon 7 in all cases so far studied.
Fusion Protein
Description Fusion of the N terminal transactivation domain of EWSR1 to the DNA binding domain of CREB1.

6. Bibliography

EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma.
Antonescu CR, Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD, Ladanyi M.
Genes Chromosomes Cancer. 2007 Dec;46(12):1051-60.
PMID 17724745
EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma.
Rossi S, Szuhai K, Ijszenga M, Tanke HJ, Zanatta L, Sciot R, Fletcher CD, Dei Tos AP, Hogendoorn PC.
Clin Cancer Res. 2007 Dec 15;13(24):7322-8.
PMID 18094413
Angiomatoid fibrous histiocytoma with t(2;22)(q33;q12.2) and EWSR1 gene rearrangement.
Shao L, Singh V, Cooley L.
Pediatr Dev Pathol. 2009 Mar-Apr;12(2):143-6.
PMID 18666823

7. Citation

This paper should be referenced as such :
Huret, JL
t(2;22)(q34;q12) in angiomatoid fibrous histiocytoma
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):994-995.
Free journal version : [ pdf ]   [ DOI ]
On line version :

8. Translocations implicated (Data extracted from papers in the Atlas)

 t(2;22)(q34;q12) EWSR1/CREB1

9. External links

Mitelman database t(2;22)(q34;q12) [CaseList]     t(2;22)(q34;q12) [Transloc - MCList]   EWSR1/CREB1 Fusion - MCList]
arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
COSMIC_fusionEWSR1 (22q12.2) CREB1 (2q33.3)    [fusion264] [fusion265] [fusion266] [fusion267] [fusion268]
Mitelman databaseEWSR1/CREB1[MCList]    EWSR1 (22q12.2) CREB1 (2q33.3)   t(2;22)(q33;q12)
TICdbEWSR1/CREB1    EWSR1 (22q12.2) CREB1 (2q33.3)
Disease databaseSoft Tissues: Angiomatoid fibrous histiocytoma with t(2;22)(q34;q12) EWSR1/CREB1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

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indexed on : Wed Nov 28 16:26:29 CET 2018

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