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t(7;8)(q34;p11) TRIM24/FGFR1

Written2006-02Elena Belloni, Francesco Lo Coco, Pier Giuseppe Pelicci
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, and IEO, Istituto Europero di Oncologia, Milan, Italy

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9967/3 Myeloid and lymphoid neoplasms with FGFR1 rearrangement
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Atlas_Id 1409

Clinics and Pathology

Disease Acute myeloid leucemia (AML) and 8p11 myeloproliferative syndrome (EMS).
Chromosome band 8p11 has been implicated in recurrent chromosome rearrangements associated either with acute myeloid leukemia (AML) or with a peculiar myeloproliferative disorder named 8p11 myeloproliferative syndrome (EMS). The latter is characterized by generalized lymphadenopathy and marked eosinophilia, rapid evolution to AML, and frequent association with non-Hodgkin lymphoma. The FGFR1 gene is constantly involved in EMS, often evolving to AML.
Phenotype / cell stem origin AML-M4 (EMS)
Clinics 1 case to date, a female patient aged 49 yrs. The differential WBC count suggested a chronic MPD. Examination of a bone marrow smear showed 44% blasts, hypoplasia, and eosinophilia. The immunophenotypic characterization revealed the coexistence of two distinct components, a myelomonocytic part along with a lymphoid population. A diagnosis of AML-M4 was established.
Treatment Induction therapy was started with daunorubicin, cytosine arabinoside, and etoposide.
Evolution The patient died of sepsis during aplasia on day 20.

Cytogenetics

 
  Genomic clones and genes in the FGFR1 (8p11) and TIF1 (7q34) regions. To the left are shown the positions of the RPCI11- 350N15 at 8p11 and of the 2 adjacent genomic clones, RPCI11-513D5 and 675F6 (vertical white bars, genes in the genomic region of interest). On the right are the positions of the 4 clones that span the TIF1 locus (indicated by a vertical white bar) at 7q34 (RPCI11-18L16, 256C24, 199L18, and 269N18).
Additional anomalies none

Genes involved and Proteins

Gene Name TRIM24
Location 7q34
Note Alias TIF1
 
  Genomic structure (not drawn to scale) of the TIF1 loci (numbered black boxes, exons) in figure a. The corresponding protein are represented in figure b.
Dna / Rna see figure a. Transcript: 2 variants. For details see the specific NCBI page.
Protein TIF1 encodes a nuclear protein, transcription intermediary factor 1a displaying an RBCC motif (RING finger, B-BOX, and coiled-coil domains, also called tripartite motif, TRIM) in its N-terminus and PHD and bromo domains at the C-terminus (figure b).
Gene Name FGFR1
Location 8p11
 
  Genomic structure (not drawn to scale) of the FGFR1 loci (numbered black boxes, exons) in figure c. The corresponding proteins are represented in figure d.
Dna / Rna see figure c. Transcript: various isoforms. For details see the specific NCBI page.
Protein The FGFR1 gene encodes the fibroblast growth factor receptor 1, a transmembrane receptor with a tyrosine kinase (TK) domain in the intracellular C-terminus, a transmembrane (TM) domain, and 3 immunoglobulin-like C-2 type extracellular domains.

Result of the chromosomal anomaly

Hybrid gene
Note TIF1-FGFR1 and FGFR1-TIF1: see figure e.
 
  
Fusion Protein
Note TIF1-FGFR1 and FGFR1-TIF1: see figure f.
 
  

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

8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes.
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Myeloproliferative disorders.
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Molecular classification and pathogenesis of eosinophilic disorders: 2005 update.
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Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.
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ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.
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Identification of four new translocations involving FGFR1 in myeloid disorders.
Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S, Parker S, Welborn J, Harris RI, Martinelli G, Montefusco V, Sinclair P, Wilkins BS, van den Berg H, Vanstraelen D, Goldman JM, Cross NC
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The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.
Walz C, Chase A, Schoch C, Weisser A, Schlegel F, Hochhaus A, Fuchs R, Schmitt-Gräff A, Hehlmann R, Cross NC, Reiter A
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Citation

This paper should be referenced as such :
Belloni, E ; Lo, Coco F ; Pelicci, PG
t(7;8)(q34;p11)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):190-193.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0708q34p11ID1409.html


Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes FGFR1 TRIM24

Translocations implicated (Data extracted from papers in the Atlas)

 t(7;8)(q34;p11) TRIM24/FGFR1

External links

TRIM24 (7q33) FGFR1 (8p11.23)

TRIM24 (7q33) FGFR1 (8p11.23)

TRIM24 (7q33) FGFR1 (8p11.23)

Mitelman databaset(7;8)(q34;p11) [Case List]    t(7;8)(q34;p11) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9967/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9975/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseTRIM24/FGFR1 [MCList]  TRIM24 (7q33) FGFR1 (8p11.23)
Mitelman databaseTRIM24/FGFR1 [MCList]  TRIM24 (7q33) FGFR1 (8p11.23)
TICdbTRIM24/FGFR1  TRIM24 (7q33) FGFR1 (8p11.23)
 
Disease databaset(7;8)(q34;p11) TRIM24/FGFR1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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