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t(5;6)(q33;q23) CEP85L/PDGFRB

Written2013-04Juliann Chmielecki, William Pao
Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA (JC); The Broad Institute of Harvard, MIT, Cancer Program, Cambridge, MA, USA (JC); Vanderbilt-Ingram Cancer Center, Department of Medicine, Nashville, TN, USA (WP)

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ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9966/3 Myeloid and lymphoid neoplasms with PDGFRB rearrangement
Atlas_Id 1620
  Karyotype analysis of the bone marrow showed a translocation involving chromosomes 5 and 6: t(5;6)(q33-34;q23).

Clinics and Pathology

Disease Precursor T-cell lymphoblastic lymphoma (T-ALL) with an association myeloproliferative neoplasm (MPN) with eosinophilia.
Epidemiology Very rare; 1 case reported (Chmielecki et al., 2011).
Clinics The patient was a 38 year-old male with a history of precursor T lymphoblastic lymphoma, a myeloid neoplasm associated neoplasm associated with eosinophilia, and a t(5;6)(q33-34;q23) identified by metaphase cytogenetics.
Treatment The patient received a brief 5-day course of imatinib therapy, prior to allogenic stem cell transplantation, which resulted in resolution of his eosinophilia (white blood cell counts decreased from 27.3 to 5.4 thou/μL; normal range (3.9-10.7 thou/μL).
Prognosis In patients with myeloid neoplasms associated with eosinophilia, imatinib is also highly active against TK fusions involving PDGFRA and PDGFRB (David et al., 2007; Vardiman et al., 2009).


The c6orf204-PDGFRB fusion protein fuses exon 11 of CEP85L/C6orf204 to exon 12 of PDGFRB. The cDNA breakpoint within PDGFRB is the same as that observed in the NIN-PDGFRB fusion, previously observed in another case of an imatinib-responsive myeloproliferative neoplasm (Vizmanos et al., 2004). The break within PDGFRB occurs just downstream of the transmembrane domain, removing the five immunoglobulin-like domains found within the extracellular domain but leaving the tyrosine kinase domain intact. The 5' sequence observed in our fusion protein could have resulted from two isoforms (a and c) arising from alternative transcriptional start sites and differing only in the first 24 amino acids. RT-PCR analysis using an anchored reverse primer and forward primers specific to isoforms a or c confirmed that the 5' sequence of the fusion originated from the isoform c start site. Motif analysis of C6orf204 revealed the presence of a coiled-coil domain just N-terminal to the breakpoint observed in the C6orf204-PDGFRB fusion. The presence of a coiled-coil domain-containing 5' partner is a common occurrence in tyrosine kinase fusions involving PDGFRB and other tyrosine kianses (Vizmanos et al., 2004), as it facilitates dimerization necessary for kinase (Carroll et al., 1996; Grisolano et al., 2003; Vizmanos et al., 2004; Taylor and Keating, 2005). The fusion here removes the last 8 amino acids of the domain. In vitro, a C6orf204-PDGFRB fusion product, generated via transient transfection of 293T cells with an expression plasmid, showed increased PDGFRB phosphorylation relative to mock transfected cells; such phosphorylation was inhibited by imatinib. Combined with the clinical response data, these studies indicate that the C6orf204-PDGFRB fusion is likely the 'driver' of the patient's eosinophilia.


Cytogenetics Molecular FISH analysis of the patient's lymph node suggested a rearrangement involving PDGFRB.
  Fluorescence in situ hybridization (FISH) of a lymph node shows one split red signal (CSF1R-PDGFRB), one normal red signal, and two normal green signals (D5S23), suggesting existence of a rearrangement involving PDGFRB (LEFT). FISH analysis with a probe against MYB on chromosome 6 (marked by CEP 6 probe) shows one copy of MYB is now located on chromosome 5, suggesting involvement of MYB in the translocation (RIGHT).
Probes FISH was performed using standard procedures with CSF1R-PDGFRB (5q31-33 region) spectrum orange, D5S23 and D5S721 (5p15.2 region) spectrum green, and MYB (6q23) spectrum aqua unique sequence DNA probes and a chromosome 6 (D6Z1) spectrum green centromere probe (Abbott Molecular, Downers Grove, IL).
Additional anomalies FISH analysis of the patient's diagnostic lymph node with T-ALL also revealed the presence of a PDGFRB rearrangement, suggesting that this event occurred in a common clonal precursor that gave rise to both the T-ALL and eosinophilia.

Genes involved and Proteins

Gene NamePDGFRB (platelet-derived growth factor receptor, beta polypeptide)
Location 5q32
Dna / Rna 23 exons.
Protein Platelet-derived growth factor receptor beta (PDGFRb) is a catalytic receptor with intrinsic intracellular tyrosine kinase activity. It plays a role in the regulation of many biological processes including embryonic development, angiogenesis, cell proliferation and differentiation, and contribute to the pathophysiology of some diseases, including cancer (adapted from GeneCards).
Gene NameCEP85L (centrosomal protein 85 like)
Location 6q22.31
Note The 5' sequence observed in our fusion protein could have resulted from two isoforms (a and c) arising from alternative transcriptional start sites and differing only in the first 24 amino acids.
Dna / Rna 13-14 exons (depending on isoform).
Protein The gene encoding CEP85L/c6orf204 was originally identified as a breast cancer antigen (Scanlan et al., 2001).

Result of the chromosomal anomaly

Hybrid gene
  Genomic structure of the in-frame c6orf204-PDGFRB fusion.
Description Exons 1-11 of c6orf204 fuse to exons 12-23 of PDGFRB.
Fusion Protein
  cDNA structure of the in-frame c6orf204-PDGFRB fusion. The resultant protein sequence is indicated below the cDNA sequence (TOP). Schematic showing the entire structure of the c6orf204-PDGFRB fusion protein including the coiled-coil domain within c6orf204 and the tyrosine kinase domain within PDGFRB.
Description Amino acids 1-677 of c6orf204 (isoform c) fused to amino acids 559-1106 of PDGFRB.
Oncogenesis The patient's clinical response to imatinib therapy suggests that this fusion is the "driver" oncogene behind the eosinophilia.

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(5;6)(q33-34;q23) in an acute myelomonocytic leukemia patient


The TEL/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways.
Carroll M, Tomasson MH, Barker GF, Golub TR, Gilliland DG.
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14845-50.
PMID 8962143
Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm.
Chmielecki J, Peifer M, Viale A, Hutchinson K, Giltnane J, Socci ND, Hollis CJ, Dean RS, Yenamandra A, Jagasia M, Kim AS, Dave UP, Thomas RK, Pao W.
Genes Chromosomes Cancer. 2012 Jan;51(1):54-65. doi: 10.1002/gcc.20930. Epub 2011 Sep 21.
PMID 21938754
Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.
David M, Cross NC, Burgstaller S, Chase A, Curtis C, Dang R, Gardembas M, Goldman JM, Grand F, Hughes G, Huguet F, Lavender L, McArthur GA, Mahon FX, Massimini G, Melo J, Rousselot P, Russell-Jones RJ, Seymour JF, Smith G, Stark A, Waghorn K, Nikolova Z, Apperley JF.
Blood. 2007 Jan 1;109(1):61-4. Epub 2006 Sep 7.
PMID 16960151
An activated receptor tyrosine kinase, TEL/PDGFbetaR, cooperates with AML1/ETO to induce acute myeloid leukemia in mice.
Grisolano JL, O'Neal J, Cain J, Tomasson MH.
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9506-11. Epub 2003 Jul 24.
PMID 12881486
Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression.
Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jager D, Chen YT, Mackay A, O'Hare MJ, Old LJ.
Cancer Immun. 2001 Mar 30;1:4.
PMID 12747765
Orientation and oligomerization specificity of the Bcr coiled-coil oligomerization domain.
Taylor CM, Keating AE.
Biochemistry. 2005 Dec 13;44(49):16246-56.
PMID 16331985
The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD.
Blood. 2009 Jul 30;114(5):937-51. doi: 10.1182/blood-2009-03-209262. Epub 2009 Apr 8. (REVIEW)
PMID 19357394
NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder.
Vizmanos JL, Novo FJ, Roman JP, Baxter EJ, Lahortiga I, Larrayoz MJ, Odero MD, Giraldo P, Calasanz MJ, Cross NC.
Cancer Res. 2004 Apr 15;64(8):2673-6.
PMID 15087377


This paper should be referenced as such :
Chmielecki, J ; Pao, W
t(5;6)(q33-34;q23) CEP85L/PDGFRB
Atlas Genet Cytogenet Oncol Haematol. 2013;17(10):718-721.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(5;6)(q33;q23) CEP85L/PDGFRB

External links

CEP85L (6q22.31) PDGFRB (5q32)

Mitelman databaset(5;6)(q33;q23)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9966/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
TICdbCEP85L/PDGFRB  CEP85L (6q22.31) PDGFRB (5q32)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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