t(8;9)(p12;q33)

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t(8;9)(p12;q33)

Identity

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)

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 ANLL 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

Location 8p12

Gene Name CEP110

Location 9q33

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.

External links

Other database t(8;9)(p12;q33) Mitelman database (CGAP - NCBI)

Other database t(8;9)(p12;q33) CancerChromosomes (NCBI)

Other database	t(8;9)(p12;q33)	Mitelman database (CGAP - NCBI)
Other database	t(8;9)(p12;q33)	CancerChromosomes (NCBI)

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

R?¬©arrangements chromosomiques et syndromes my?¬©loprolif?¬©ratifs mixtes.

Popovici C

Thˆ®se Aix Marseille II,. 1998.

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, Pˆ©busque MJ

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

PMID 10688839

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

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

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

Contributor(s)

Written 01-2004 Jacques Boyer

Citation

This paper should be referenced as such :
Boyer J . t(8;9)(p12;q33). Atlas Genet Cytogenet Oncol Haematol. January 2004 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t0809p12q33ID1129.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon May 12 18:12:36 2008

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For comments and suggestions or contributions, please contact us

j.l.huret@chu-poitiers.fr.

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 ANLL 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	CEP110
Location	9q33
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.