t(6;8)(q27;p12) FGFR1OP/FGFR1

2007-05-01   José Luis Vizmanos 

1.Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

Clinics and Pathology


BCR-ABL negative chronic myeloproliferative disease associates with 8p11 chromosomal rearrangements and a clinical entity named "8p11 myeloproliferative syndrome" (EMS) or "stem cell leukemia/lymphoma" (SCLL) syndrome. These chromosomal rearrangements fuse FGFR1 (a receptor tyrosine kinase gene) with other genes resulting in new chimeric genes which are translated in constitutionally activated FGFR1-like proteins. This is a multilineage disorder with combined occurrence of myeloid malignancy and T- cell NHL, or myeloid metaplasia.

Phenotype stem cell origin

The same t(6;8)(q27;p12) is found both in the bone marrow and in the lymph node: the multilineage involvement suggests the malignant transformation of a primitive hematopoietic stem cell.


Rare, very few cases described with this translocation (eight until date, four female and four male). A higher number have been described with other FGFR1 fusions, mainly t(8;13) and ZNF198-FGFR1 fusion.


This is a myeloproliferative aggressive disease; complex picture of myeloid hyperplasia progressing to myelodysplasia and T- lymphoma, and acute myeloid leukemia; enlarged lymph node infiltrated by myeloid blast cells; blood data: high WBC (median 40 X 109/l); myelemia; monocytosis and eosinophilia. The clinical phenotype at presentation may vary between different partner genes involved in the FGFR1 fusion and, furthermore, between individuals.
Only eight cases with the t(6;8)(q27;p11) have been reported. Four of these patients had features at presentation and/or a clinical course typical of EMS: malignant T-cell lymphoma and CML, AML/myeloproliferative disease, CML-like disease with eosinophilia that progressed rapidly to AML, and primary AML that evolved to EMS following chemotherapy. Two cases presented with polycytemia vera (PV), one of them progressed to AML after a period of 5 years and the other one progressed to an EMS-like myeloproliferative disorder. The remaining case reported showed a B-ALL at presentation. This phenotype has been also described in the transformation phase of some cases with other FGFR1 fusions.


EMS or SCLL seems to be refractory to conventional chemotherapy and some good results have been reached with allogeneic stem cell transplantation. Imatinib is not effective against constitutional activated FGFR1, but this disease could be responsive to specific FGFR1 inhibitors.


CR could be obtained, but is promptly followed by relapse progressing rapidly to an AML, rarely ALL.


Median survival: 6 months. Although the number of reported cases is low, EMS seems to be disease with bad prognosis that generally progresses to acute leukemia.


Cytogenetics morphological

Available data shows that sometimes the t(6;8)(q27;p12) is not the sole abnormality.BM: 46,XX,t(6;8)(6pter-6q27::8p12-8pter;6qter-6q27::8p12-8qter)BM: 46,XY,t(6;8)(q27;p11) [100%]BM: 46,XY,t(6;8)(q27;p11) [100%]BM: 46,XY,t(6;8)(q27;p11.2)BM: 46,XX,t(6;8)(q27;p11.2),+8,+10,-18,-19,+dic(18;19)(p11.2;p13.3)BM: 46,XX,t(6;8)(q27;p12),+der(6)add(6)(q27) [66% ]; 46,XX,t(6;8)(q27;p12) [34%]BM: 45,XY,t(6;8)(q27;p12),-7 [100%]

Cytogenetics molecular

Mega YAC 959-A -4 (1260kb) from CEPH; FGFR1-specific cosmid 134.8


t(6;8)(q27;p12) is one of the reported rearrangements of 8p11 that fuses FGFR1 with other partner genes.

Genes Involved and Proteins

Gene name
FGFR1 (Fibroblast Growth Factor Receptor 1)
This gene is involved in several fusions.
Dna rna description
24 exons spanning about 55.9 Kb on 8p12. Transcription is from centromere to telomere. Based on Entrez data, FGFR1OP has seven different transcripts. Based on EnsEMBL data it has five different transcripts.
Protein description
According to UniProt-SwissProt FGFR1 (FGFR1_HUMAN) or fibroblast growth factor receptor 1 is a receptor for basic fibroblast growth factor located in the membrane. Binding of FGF1 and heparin promotes autophosphorylation on tyrosine residues and activation of the receptor. FGFR1 contains 3 Ig-like C2-type (immunoglobulin-like) domains and a protein kinase domain. It belongs to the protein tyrosine kinase family, fibroblast growth factor receptor subfamily.
Defects in FGFR1 have been associated with Pfeiffer syndrome (PS) or acrocephalosyndactyly type V (ACS5), hypogonadotropic hypogonadism (IHH), Kallmann syndrome type 2 (KAL2) ; osteoglophonic dysplasia (OGD) ; or osteoglophonic dwarfism, non-syndromic trigonocephaly or metopic craniosynostosis, and the EMS/SCLL due to fusion with other genes and constitutive activation of this receptor.
Gene name
FGFR1OP (FGFR1 oncogene partner)
This gene is involved only in this fusion.
Dna rna description
13 exons spanning about 43.2 Kb on 6q27. Transcription is from centromere to telomere. Based on Entrez data, FGFR1OP has two different transcripts. Based on EnsEMBL-Vega data it has up to 6 different transcripts.
Protein description
According to UniProt-SwissProt FGFR1OP (FR1OP_HUMAN) is a centrosomal protein associated with gamma-tubulin and required for anchoring microtubules to the centrosomes. Other centrosomal proteins have been described as fusion partner of tyrosine kinases like FGFR1.
Protein description
FGFR1OP is a hydrophilic protein that contains several leucine-rich regions with consensus sequences L-X2-L-X3­5-L-X3­5-L (in some of them leucine is substituted by either valine or isoleucine) in its amino and carboxy termini. It has a putative role as a regulator of normal proliferation and differentiation of the erythroid lineage and could belong to a novel family of the leucine-rich proteins. FGFR1OP also contains a Lis-homology (LisH) motif found in more than 100 eukaryotic proteins. These motifs are believed to be involved in microtubule dynamics and organization, cell migration and chromosome segregation; several of them are associated with genetic diseases.
Protein description
Its expression is ubiquitous but is higher in heart, liver, muscle, kidney, intestine, colon, adrenal gland, prostate, testis, and pancreas.

Result of the Chromosomal Anomaly

Atlas Image
Schematic representation of the fusion FGFR1OP-FGFR1 resulting from the t(6;8)(q27;p12). Top figure courtesy José Luis Vizmanos : From top to bottom: structure of FGFR1, FGFR1OP and the putative chimeric FGFR1OP-FGFR1. TM, transmembrane domain; TK, tyrosine kinase domain. The breakpoints on FGFR1OP are variable as described in refs. 4, 5 and 10; Bottom figure courtesy Marie-Josèphe Pébusque


Three different hybrid genes have been described, based on different breakpoints on the FGFR1OP gene. An in-frame fusion between FGFR1OP exon 6 and FGFR1 exon 9 was described; later, two variants in different patients, both in-frame with FGFR1 exon 9, one of them involving FGFR1OP exon 5 and the other involving FGFR1OP exon 7 was described. The presence of two different transcripts (one with a breakpoint in FGFR1OP exon 6 and the other with a breakpoint in exon 7) was reported.



Detection protocole

See ref. 4 below.


The fusion gene is predicted to encode an aberrant tyrosine kinase composed of the putative leucine-rich N-terminal region of FOP, and the FGFR1 intracellular region. Like other fusions involving RTKs, FGFR1OP-FGFR1 lacks the FGFR1 transmembrane domain.


Through constitutive activation of FGFR1 signal transduction pathways, via putative dimerization of the fusion protein via the FOP leucine-rich repeats FGFR1OP shares features in common with other tyrosine kinase fusion partners, namely widespread expression and the presence of putative oligomerization domains. There is experimental proof that expression of FOP-FGFR1 in primary bone marrow cells induced by retroviral transduction generates a rapid MPD in mice. However, lymphoproliferation and progression to acute phase were not observed in the murine model.

Highly cited references

Pubmed IDYearTitleCitations
272451472016FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review).130
155702992004Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases.8


Pubmed IDLast YearTitleAuthors
94847861998t(6;8), t(8;9) and t(8;13) translocations associated with stem cell myeloproliferative disorders have close or identical breakpoints in chromosome region 8p11-12.Chaffanet M et al
79938121994Detection and significance of bone marrow infiltration at the time of autologous bone marrow transplantation in Hodgkin's disease.Chopra R et al
120942442002Tyrosine kinase fusion genes in chronic myeloproliferative diseases.Cross NC et al
129699582004FOP-FGFR1 tyrosine kinase, the product of a t(6;8) translocation, induces a fatal myeloproliferative disease in mice.Guasch G et al
119193912002The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1.Macdonald D et al
166900812006Structure of the N-terminal domain of the FOP (FGFR1OP) protein and implications for its dimerization and centrosomal localization.Mikolajka A et al
99491821999The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1.Popovici C et al
119193892002Sequential transformation of t(8;13)-related disease: a case report.Roy S et al
115502832001Identification of four new translocations involving FGFR1 in myeloid disorders.Sohal J et al
65909321984Simultaneous occurrence of a T-cell lymphoma and a chronic myelogenous leukemia with an unusual karyotype.Vannier JP et al
155702992004Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases.Vizmanos JL et al
168796082006A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene.Yamamoto K et al
163143882006A complex of two centrosomal proteins, CAP350 and FOP, cooperates with EB1 in microtubule anchoring.Yan X et al


Fusion gene

FGFR1OP/FGFR1 FGFR1OP (6q27) FGFR1 (8p11.23) M t(6;8)(q27;p11)
Atlas Image
G-band analysis. Partial karyotype showing the t(6;8)(q27;p12); courtesy José Luis Vizmanos.


José Luis Vizmanos

t(6;8)(q27;p12) FGFR1OP/FGFR1

Atlas Genet Cytogenet Oncol Haematol. 2007-05-01

Online version: http://atlasgeneticsoncology.org/haematological/1090/t(6;8)(q27;p12)

Historical Card

2000-12-01 t(6;8)(q27;p12) FGFR1OP/FGFR1 by  Marie-Josçphe Pébusque