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t(2;8)(q12;p11) RANBP2/FGFR1

Written2014-11Carine Gervais
Laboratoire de Cytogenetique Hematologique, CHU Strasbourg, 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 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1661

Clinics and Pathology

Disease Myeloid and lymphoid neoplasms with FGFR1 abnormalities (previously: 8p11 myeloproliferative syndrome)
Note Different disease phenotypes according to the FGFR1 partner gene.
Phenotype / cell stem origin Pluripotent haematopoietic stem cell.
Epidemiology Only one case to date, a 63 years old female with myeloproliferative/myelodysplastic neoplasm (Gervais et al., 2013).
Clinics Splenomegaly, dyspnea, impaired general condition at diagnosis. Rapid disease progression despite chemotherapy.
 
Bone marrow (MGG): hypercellularity with granular hyperplasia, dysgranulopoiesis and few eosinophils.
Evolution Disease progressed rapidly and the patient died 6 months after the diagnosis.
Prognosis Undetermined (myeloid and lymphoid neoplasms with FGFR1 abnormalities prognosis is currently poor).

Cytogenetics

Cytogenetics Morphological t(2;8)(q12;p11) without additional abnormality.
 
  R and G-banding showing t(2;8)(q12;p11).
 
  Cohybridization of FGFR1 BAC RP11-350N15 (8p11, green) and RANBP2 RP11-84C2 (2q12, red) showing a dual fusion signal.

Genes involved and Proteins

Gene Name FGFR1
Location 8p11.23
Note Receptor tyrosine kinase.
Dna / Rna 18 exons.
Protein Extracellular ligand-binding domain (with the N-terminus). Unique transmembrane domain. Catalytic (tyrosine kinase) cytosolic domain.
Gene Name RANBP2
Location 2q12.3
Note Implicated in various cancers, inflammatory myofibroblastic tumors (with ALK 2p23), JMML and AML with RANBP2-ALK fusion (Rottgers et al., 2010; Maesako et al., 2014; Lim et al., 2014).
Dna / Rna 31 exons.
Protein Component of the nuclear pore complex, localised at its cytoplasmic side.

Result of the chromosomal anomaly

Hybrid gene
  Schematic representation of RANBP2-FGFR1 fusion transcript.
 
Description 5' RANBP2 - 3' FGFR1; fusion of RANPB2 exon 20 to FGFR1 exon 9.
Transcript Detection of both RANBP2-FGFR1 transcript and FGFR1-RANBP2 reciprocal transcript.
  
Fusion Protein
 
  Schematic representation of RANBP2, FGFR1 and RANBP2-FGFR1 predicted fusion protein.
Description RANBP2 N-terminal (leucine-rich region) - FGFR1 C-terminal (TK domain).
Oncogenesis Constitutive activation of FGFR1 kinase activity.
  

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 Mar;42(3):320-5.
PMID 15609342
 
The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins.
Demiroglu A, Steer EJ, Heath C, Taylor K, Bentley M, Allen SL, Koduru P, Brody JP, Hawson G, Rodwell R, Doody ML, Carnicero F, Reiter A, Goldman JM, Melo JV, Cross NC.
Blood. 2001 Dec 15;98(13):3778-83.
PMID 11739186
 
Fusion of the BCR and the fibroblast growth factor receptor-1 (FGFR1) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: the first fusion gene involving BCR but not ABL.
Fioretos T, Panagopoulos I, Lassen C, Swedin A, Billstrom R, Isaksson M, Strombeck B, Olofsson T, Mitelman F, Johansson B.
Genes Chromosomes Cancer. 2001 Dec;32(4):302-10.
PMID 11746971
 
A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm.
Gervais C, Dano L, Perrusson N, Helias C, Jeandidier E, Galoisy AC, Ittel A, Herbrecht R, Bilger K, Mauvieux L.
Leukemia. 2013 Apr;27(5):1186-8. doi: 10.1038/leu.2012.286. Epub 2012 Oct 8.
PMID 23041776
 
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 May;40(1):78-83.
PMID 15034873
 
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, Pebusque MJ.
Blood. 2000 Mar 1;95(5):1788-96.
PMID 10688839
 
Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3).
Guasch G, Popovici C, Mugneret F, Chaffanet M, Pontarotti P, Birnbaum D, Pebusque MJ.
Blood. 2003 Jan 1;101(1):286-8. Epub 2002 Jun 28.
PMID 12393597
 
The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1.
Hidalgo-Curtis C, Chase A, Drachenberg M, Roberts MW, Finkelstein JZ, Mould S, Oscier D, Cross NC, Grand FH.
Genes Chromosomes Cancer. 2008 May;47(5):379-85. doi: 10.1002/gcc.20541.
PMID 18205209
 
Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome.
Li F, Zhai YP, Tang YM, Wang LP, Wan PJ.
Genes Chromosomes Cancer. 2012 Sep;51(9):890-7. doi: 10.1002/gcc.21973. Epub 2012 May 23.
PMID 22619110
 
Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement: a report of two cases and literature review.
Li J, Yin WH, Takeuchi K, Guan H, Huang YH, Chan JK.
Diagn Pathol. 2013 Sep 13;8:147. doi: 10.1186/1746-1596-8-147. (REVIEW)
PMID 24034896
 
RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia.
Lim JH, Jang S, Park CJ, Cho YU, Lee JH, Lee KH, Lee JO, Shin JY, Kim JI, Huh J, Seo EJ.
Cancer Genet. 2014 Jan-Feb;207(1-2):40-5. doi: 10.1016/j.cancergen.2013.12.003. Epub 2014 Jan 21. (REVIEW)
PMID 24613277
 
Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor.
Ma Z, Hill DA, Collins MH, Morris SW, Sumegi J, Zhou M, Zuppan C, Bridge JA.
Genes Chromosomes Cancer. 2003 May;37(1):98-105.
PMID 12661011
 
inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman.
Maesako Y, Izumi K, Okamori S, Takeoka K, Kishimori C, Okumura A, Honjo G, Akasaka T, Ohno H.
Int J Hematol. 2014 Feb;99(2):202-7. doi: 10.1007/s12185-013-1482-x. Epub 2013 Dec 4.
PMID 24307515
 
The 8p12 myeloproliferative disorder. t(8;19)(p12;q13.3): a novel translocation involving the FGFR1 gene.
Mugneret F, Chaffanet M, Maynadie M, Guasch G, Favre B, Casasnovas O, Birnbaum D, Pebusque MJ.
Br J Haematol. 2000 Nov;111(2):647-9.
PMID 11122115
 
The 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, Zhang B, Gregoire MJ, Jonveaux P, Lafage-Pochitaloff M, Birnbaum D, Pebusque MJ.
Blood. 1999 Feb 15;93(4):1381-9.
PMID 9949182
 
ALK fusion genes in children with atypical myeloproliferative leukemia.
Rottgers S, Gombert M, Teigler-Schlegel A, Busch K, Gamerdinger U, Slany R, Harbott J, Borkhardt A.
Leukemia. 2010 Jun;24(6):1197-200. doi: 10.1038/leu.2010.18. Epub 2010 Apr 29.
PMID 20428197
 
LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome.
Soler G, Nusbaum S, Varet B, Macintyre EA, Vekemans M, Romana SP, Radford-Weiss I.
Leukemia. 2009 Jul;23(7):1359-61. doi: 10.1038/leu.2009.79. Epub 2009 Apr 16.
PMID 19369959
 
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-Graff A, Hehlmann R, Cross NC, Reiter A.
Leukemia. 2005 Jun;19(6):1005-9.
PMID 15800673
 
The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11).
Wasag B, Lierman E, Meeus P, Cools J, Vandenberghe P.
Haematologica. 2011 Jun;96(6):922-6. doi: 10.3324/haematol.2010.036558. Epub 2011 Feb 17.
PMID 21330321
 
FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.
Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, Stone R, Weissman SM, Hudson TJ, Fletcher JA.
Nat Genet. 1998 Jan;18(1):84-7.
PMID 9425908
 

Citation

This paper should be referenced as such :
Gervais C
t(2;8)(q12;p11) RANBP2/FGFR1;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0208q12p11ID1661.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(2;8)(q12;p11) RANBP2/FGFR1

External links

Mitelman databaset(2;8)(q12;p11) [Case List]    t(2;8)(q12;p11) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9967/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(2;8)(q12;p11) RANBP2/FGFR1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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