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

2006-02-01 Elena Belloni , Francesco Lo Coco , Pier Giuseppe Pelicci Affiliation

1.IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, and IEO, Istituto Europero di Oncologia, Milan, Italy

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 stem cell 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 (tripartite motif-containing 24)

Location

7q33

Note

Alias TIF1

Dna rna description

see figure a. Transcript: 2 variants. For details see the specific NCBI page.

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.

Protein description

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 (Fibroblast Growth Factor Receptor 1)

Location

8p11.23

Dna rna description

see figure c. Transcript: various isoforms. For details see the specific NCBI page.

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.

Protein description

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

Note

TIF1-FGFR1 and FGFR1-TIF1: see figure e.

Note

TIF1-FGFR1 and FGFR1-TIF1: see figure f.

Bibliography

Pubmed ID	Last Year	Title	Authors
15609342	2005	8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes.	Belloni E et al
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10640219	1998	Molecular genetics and cytogenetics of myeloproliferative disorders.	Bench AJ et al
15995322	2005	Molecular classification and pathogenesis of eosinophilic disorders: 2005 update.	Gotlib J et al
16781488	2006	Eosinophilic disorders: molecular pathogenesis, new classification, and modern therapy.	Gotlib J et al
15034873	2004	Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.	Grand EK et al
16946300	2006	Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia.	Gu TL et al
14660670	2004	Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1.	Heath C et al
9889006	1999	The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome.	Kulkarni S et al
11919391	2002	The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1.	Macdonald D et al
9716603	1998	Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome.	Reiter A et al
10373756	1999	[The 8p11 myeloproliferative syndrome].	Reither A et al
15050920	2004	Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations.	Roumiantsev S et al
10935490	1999	ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.	Smedley D et al
11550283	2001	Identification of four new translocations involving FGFR1 in myeloid disorders.	Sohal J et al
15995325	2005	Modern diagnosis and treatment of primary eosinophilia.	Tefferi A et al
15570299	2004	Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases.	Vizmanos JL et al
15800673	2005	The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.	Walz C et al
16777224	2007	Clonal evolution of 8p11 stem cell syndrome in a 14-year-old Chinese boy: a review of literature of t(8;13) associated myeloproliferative diseases.	Wong WS et al
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Summary

Fusion gene

TRIM24/FGFR1 TRIM24 (7q33) FGFR1 (8p11.23) M|TRIM24/FGFR1 TRIM24 (7q33) FGFR1 (8p11.23) M t(7;8)(q34;p11)|TRIM24/FGFR1 TRIM24 (7q33) FGFR1 (8p11.23) TIC

Citation

Elena Belloni ; Francesco Lo Coco ; Pier Giuseppe Pelicci

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

Atlas Genet Cytogenet Oncol Haematol. 2006-02-01

Online version: http://atlasgeneticsoncology.org/haematological/1409/t(7;8)(q34;p11)