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

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 (tripartite motif-containing 24)
Location	7q33
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 (Fibroblast Growth Factor Receptor 1)
Location	8p11.23
	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.

Belloni E, Trubia M, Gasparini P, Micucci C, Tapinassi C, Confalonieri S, Nuciforo P, Martino B, Lo-Coco F, Pelicci PG, Di Fiore PP

Genes, chromosomes & cancer. 2005 ; 42 (3) : 320-325.

PMID 15609342

Myeloproliferative disorders.

Bench AJ, Cross NC, Huntly BJ, Nacheva EP, Green AR

Best practice & research. Clinical haematology. 2001 ; 14 (3) : 531-551.

PMID 11640868

Molecular genetics and cytogenetics of myeloproliferative disorders.

Bench AJ, Nacheva EP, Champion KM, Green AR

Bailliere's clinical haematology. 1998 ; 11 (4) : 819-848.

PMID 10640219

Molecular classification and pathogenesis of eosinophilic disorders: 2005 update.

Gotlib J

Acta haematologica. 2005 ; 114 (1) : 7-25.

PMID 15995322

Eosinophilic disorders: molecular pathogenesis, new classification, and modern therapy.

Gotlib J, Cross NC, Gilliland DG

Best practice & research. Clinical haematology. 2006 ; 19 (3) : 535-569.

PMID 16781488

Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.

Grand EK, Grand FH, Chase AJ, Ross FM, Corcoran MM, Oscier DG, Cross NC

Genes, chromosomes & cancer. 2004 ; 40 (1) : 78-83.

PMID 15034873

Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia.

Gu TL, Goss VL, Reeves C, Popova L, Nardone J, Macneill J, Walters DK, Wang Y, Rush J, Comb MJ, Druker BJ, Polakiewicz RD

Blood. 2006 ; 108 (13) : 4202-4204.

PMID 16946300

Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1.

Heath C, Cross NC

The Journal of biological chemistry. 2004 ; 279 (8) : 6666-6673.

PMID 14660670

The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome.

Kulkarni S, Reiter A, Smedley D, Goldman JM, Cross NC

Genomics. 1999 ; 55 (1) : 118-121.

PMID 9889006

The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1.

Macdonald D, Reiter A, Cross NC

Acta haematologica. 2002 ; 107 (2) : 101-107.

PMID 11919391

Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome.

Reiter A, Sohal J, Kulkarni S, Chase A, Macdonald DH, Aguiar RC, Gonçalves C, Hernandez JM, Jennings BA, Goldman JM, Cross NC

Blood. 1998 ; 92 (5) : 1735-1742.

PMID 9716603

[The 8p11 myeloproliferative syndrome]

Reither A, Hehlmann R, Goldman JM, Cross NC

Medizinische Klinik (Munich, Germany : 1983). 1999 ; 94 (4) : 207-210.

PMID 10373756

Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations.

Roumiantsev S, Krause DS, Neumann CA, Dimitri CA, Asiedu F, Cross NC, Van Etten RA

Cancer cell. 2004 ; 5 (3) : 287-298.

PMID 15050920

ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.

Smedley D, Demiroglu A, Abdul-Rauf M, Heath C, Cooper C, Shipley J, Cross NC

Neoplasia (New York, N.Y.). 1999 ; 1 (4) : 349-355.

PMID 10935490

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

Genes, chromosomes & cancer. 2001 ; 32 (2) : 155-163.

PMID 11550283

Modern diagnosis and treatment of primary eosinophilia.

Tefferi A

Acta haematologica. 2005 ; 114 (1) : 52-60.

PMID 15995325

Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases.

Vizmanos JL, Hernández R, Vidal MJ, Larráyoz MJ, Odero MD, Marín J, Ardanaz MT, Calasanz MJ, Cross NC

The hematology journal : the official journal of the European Haematology Association / EHA. 2004 ; 5 (6) : 534-537.

PMID 15570299

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

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (6) : 1005-1009.

PMID 15800673

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, Cheng KC, Lau KM, Chan NP, Shing MM, Cheng SH, Chik KW, Li CK, Ng MH

Leukemia research. 2007 ; 31 (2) : 235-238.

PMID 16777224

A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene.

Yamamoto K, Kawano H, Nishikawa S, Yakushijin K, Okamura A, Matsui T

European journal of haematology. 2006 ; 77 (4) : 349-354.

PMID 16879608

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 database	t(7;8)(q34;p11) [Case List]    t(7;8)(q34;p11) [Transloc-MCList] TRIM24/FGFR1 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)	Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Topo ( C42) Morph ( 9967/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Topo ( C42) Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman database	TRIM24/FGFR1 [MCList]  TRIM24 (7q33) FGFR1 (8p11.23)
Mitelman database	TRIM24/FGFR1 [MCList]  TRIM24 (7q33) FGFR1 (8p11.23)
TICdb	TRIM24/FGFR1  TRIM24 (7q33) FGFR1 (8p11.23)

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