t(8;9)(p12;q33) CNTRL/FGFR1

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t(8;9)(p12;q33) CNTRL/FGFR1

Written	2004-01	Jacques Boyer
		Laboratoire d' hématologie, CH du MANS, France

(Note : for Links provided by Atlas : click)

Identity

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

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 1129

Note 8p12 myeloproliferative syndrome (EMS) / stem cell leukemia-lymphoma syndrome (SCLL) belongs to the tyrosine kinase fusion genes chronic myeloproliferative diseases .
It is associated with recurent translocations :
t(6;8)(q27;p12),
t(8;9)(p12;q33),
t(8;11)(p12;p15),
t(8;12)(p12;q15),
t(8;13)(p12;q12),
t(8;17)(p12;q25),
t(8;19)(p12;q13),
t(8;22)(p12;q11)

t(8;9)(p12;q33) - Courtesy Melanie Zenger and Claudia Haferlachxi

Clinics and Pathology

Disease Myeloproliferative disorder that is frequently associated with T-cell, or less commonly B-cell non Hodgkin lymphoma.

Phenotype / cell stem origin May involve a stem cell.

Epidemiology 9 cases are described ; sexe ratio : 6M/3F.

Clinics Agressive disease ; myeloid hyperplasia progressing to myelodysplasia and T or B-cell lymphoma, splenomegaly, lymph node.
High WBC with myelemia with frequently eosinophilia and sometimes monocytosis (near CMLL).

Evolution The disease transforms to AML or occasionally ALL in a median of 6 months.

Prognosis Median survival : 12 months.

Cytogenetics

Cytogenetics Morphological This translocation is a variant of the t(8 ;13)(p12 ;q12).

Additional anomalies +der(9), +21

Genes involved and Proteins

Gene Name FGFR1 (Fibroblast Growth Factor Receptor 1)

Location 8p11.23

Gene Name CNTRL (centriolin)

Location 9q33.2

Dna / Rna DNA : 26kb - 19 exons
RNA : Three mains transcripts of approximatly 7.5, 4.5 and 1.5 kb. CEP transcripts are barely expressed in thymus and peripheral blood cells.

Protein CEP110 gene codes for a 994-amino acid coiled-coil protein with 4 consensus leucine zippers (centrosome associated P110 protein).

Result of the chromosomal anomaly

Hybrid gene
Description The t(8;9) breakpoint in the FGFR1 gene is localized in exon 8, 12 bp upstream of the exon 8/intron 8 junction. It is distinct from the breakpoints in the t(6;8) and t(8;13) but it preserves the same FGFR1 sequence in the chimeric protein.
The breakpoint in the CEP110 is localized in exon 15.
The translocation leads to the formation of the two reciprocal transcripts.

Fusion Protein
Description
The CEP110-FGFR1 fusion protein encodes an aberrant tyrosine kinase of 150-kd wich retains most of CEP110 with the leucine zipper motif and the catalytic domain of FGFR1.
The CEP110-FGFR1 protein has a constitutive kinase activity and is located within the cell cytoplasm contrasting with the centrosome and membrane localizations of the wildtype respective proteins.
The FGFR1-CEP110 protein contains the FGFR1 N-terminal region with its ligand-binding and transmembrane domains and the CEP110 C-terminal region.

Oncogenesis Activated aberrant tyrosine kinase are likely to promote leukemogenesis through contitutive activation of the FGFR1 kinase. This activation may be mediated by dimerisation of the portion of the fusion protein wich contains the leucine zippers.
This activation may interacts with the cell proliferation and the apoptose, additional anomalies may also play an important role in the evolution of the disease.

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.

Case Report Translocation t(8;9)(p12;q33) detected in cALL: A case report

Bibliography

Tyrosine kinase fusion genes in chronic myeloproliferative diseases.

Cross NC, Reiter A

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (7) : 1207-1212.

PMID 12094244

FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).

Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pébusque MJ

Blood. 2000 ; 95 (5) : 1788-1796.

PMID 10688839

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

R?éarrangements chromosomiques et syndromes my?éloprolif?é mixtes.

Popovici C

Thè Aix Marseille II,. 1998.

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

Citation

This paper should be referenced as such :

Boyer, J

t(8;9)(p12;q33)

Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):92-93.

Free journal version : [ pdf ] [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Anomalies/t0809p12q33ID1129.html

Translocations implicated (Data extracted from papers in the Atlas)

t(8;9)(p12;q33) CNTRL/FGFR1

External links

CNTRL (9q33.2) FGFR1 (8p11.23)
CNTRL (9q33.2) FGFR1 (8p11.23)
CNTRL (9q33.2) FGFR1 (8p11.23)
Mitelman database t(8;9)(p12;q33) [Case List]    t(8;9)(p12;q33) [Transloc-MCList] CNTRL/FGFR1 [Fusion-MCList]
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 CNTRL/FGFR1 [MCList]  CNTRL (9q33.2) FGFR1 (8p11.23)

Mitelman database CNTRL/FGFR1 [MCList]  CNTRL (9q33.2) FGFR1 (8p11.23)

TICdb CNTRL/FGFR1  CNTRL (9q33.2) FGFR1 (8p11.23)

REVIEW articles automatic search in PubMed

Last year articles automatic search in PubMed

All articles automatic search in PubMed

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For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.

ICD-Topo	C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
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	1129
Note	8p12 myeloproliferative syndrome (EMS) / stem cell leukemia-lymphoma syndrome (SCLL) belongs to the tyrosine kinase fusion genes chronic myeloproliferative diseases . It is associated with recurent translocations : t(6;8)(q27;p12), t(8;9)(p12;q33), t(8;11)(p12;p15), t(8;12)(p12;q15), t(8;13)(p12;q12), t(8;17)(p12;q25), t(8;19)(p12;q13), t(8;22)(p12;q11)


	t(8;9)(p12;q33) - Courtesy Melanie Zenger and Claudia Haferlachxi

Disease	Myeloproliferative disorder that is frequently associated with T-cell, or less commonly B-cell non Hodgkin lymphoma.
Phenotype / cell stem origin	May involve a stem cell.
Epidemiology	9 cases are described ; sexe ratio : 6M/3F.
Clinics	Agressive disease ; myeloid hyperplasia progressing to myelodysplasia and T or B-cell lymphoma, splenomegaly, lymph node. High WBC with myelemia with frequently eosinophilia and sometimes monocytosis (near CMLL).
Evolution	The disease transforms to AML or occasionally ALL in a median of 6 months.
Prognosis	Median survival : 12 months.

Cytogenetics Morphological	This translocation is a variant of the t(8 ;13)(p12 ;q12).
Additional anomalies	+der(9), +21

Gene Name	FGFR1 (Fibroblast Growth Factor Receptor 1)
Location	8p11.23

Gene Name	CNTRL (centriolin)
Location	9q33.2
Dna / Rna	DNA : 26kb - 19 exons RNA : Three mains transcripts of approximatly 7.5, 4.5 and 1.5 kb. CEP transcripts are barely expressed in thymus and peripheral blood cells.
Protein	CEP110 gene codes for a 994-amino acid coiled-coil protein with 4 consensus leucine zippers (centrosome associated P110 protein).

Description	The t(8;9) breakpoint in the FGFR1 gene is localized in exon 8, 12 bp upstream of the exon 8/intron 8 junction. It is distinct from the breakpoints in the t(6;8) and t(8;13) but it preserves the same FGFR1 sequence in the chimeric protein. The breakpoint in the CEP110 is localized in exon 15. The translocation leads to the formation of the two reciprocal transcripts.

Description	The CEP110-FGFR1 fusion protein encodes an aberrant tyrosine kinase of 150-kd wich retains most of CEP110 with the leucine zipper motif and the catalytic domain of FGFR1. The CEP110-FGFR1 protein has a constitutive kinase activity and is located within the cell cytoplasm contrasting with the centrosome and membrane localizations of the wildtype respective proteins. The FGFR1-CEP110 protein contains the FGFR1 N-terminal region with its ligand-binding and transmembrane domains and the CEP110 C-terminal region.
Oncogenesis	Activated aberrant tyrosine kinase are likely to promote leukemogenesis through contitutive activation of the FGFR1 kinase. This activation may be mediated by dimerisation of the portion of the fusion protein wich contains the leucine zippers. This activation may interacts with the cell proliferation and the apoptose, additional anomalies may also play an important role in the evolution of the disease.

	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.
Case Report	Translocation t(8;9)(p12;q33) detected in cALL: A case report

Mitelman database	t(8;9)(p12;q33) [Case List] t(8;9)(p12;q33) [Transloc-MCList] CNTRL/FGFR1 [Fusion-MCList]
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	CNTRL/FGFR1 [MCList] CNTRL (9q33.2) FGFR1 (8p11.23)
Mitelman database	CNTRL/FGFR1 [MCList] CNTRL (9q33.2) FGFR1 (8p11.23)
TICdb	CNTRL/FGFR1 CNTRL (9q33.2) FGFR1 (8p11.23)

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed
All articles	automatic search in PubMed