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ins(9;4)(q33;q12q25) CDK5RAP2::PDGFRA

Written2010-03Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Atlas_Id 1450

Clinics and Pathology

Disease Chronic eosinophilic leukemia
Epidemiology One case to date, a 71-year-old female patient with chronic eosinophilic leukemia in accelerated phase (Walz et al., 2006)..
Prognosis Remission was obtained with imatinib, but the patient relapsed with imatinib-resistant acute myeloid leukemia that was characterized by a normal karyotype, absence of detectable CDK5RAP2-PDGFRA mRNA, and a newly acquired G12D NRAS mutation.

Genes involved and Proteins

Gene NamePDGFRA (platelet-derived growth factor receptor, alpha polypeptide)
Location 4q12
Protein Receptor tyrosine kinase. Gain-of-function mutations of PDGFRA are implicated in a subset of gastrointestinal stromal tumors (Heinrich et al., 2003). PDGFRA has also been involved in translocations, making hybrid genes with STRN (2p22), FIP1L1 (4q12), KIF5B (10p11), ETV6 (12p13) and BCR (22q11).
Gene NameCDK5RAP2 (CDK5 regulatory subunit associated protein 2)
Location 9q33.2
Protein Centrosomal protein; regulates CDK5; binds EB1. The CDK5RAP2-EB1 complex stimulates microtubule assembly (Fong et al., 2009); critical for centrosomal localization of dynein throughout the cell cycle (Lee and Rhee, 2010). CDK5RAP2-knockdown cells have increased resistance to paclitaxel and doxorubicin (Zhang et al., 2009). Homozygous mutations in CDK5RAP2 can cause microcephaly (Bond et al., 2005).

Result of the chromosomal anomaly

Hybrid gene
Description In-frame fusion between exon 13 of the CDK5RAP2, a 40 bp insert from an inverted sequence of PDGFRA intron 9, and a truncated PDGFRA exon 12. No reciprocal PDGFRA-CDK5RAP2 transcript.
Fusion Protein
Description N-term CDK5RAP2 - C-term PDGFRA; 1003 amino acids; contains 494 amino acids, including several potential dimerization domains, of CDK5RAP2 and 509 amino acids from PDGFRA tyrosine kinase domains.
Oncogenesis Constitutive tyrosine kinase activity is likely.

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.


A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size.
Bond J, Roberts E, Springell K, Lizarraga SB, Scott S, Higgins J, Hampshire DJ, Morrison EE, Leal GF, Silva EO, Costa SM, Baralle D, Raponi M, Karbani G, Rashid Y, Jafri H, Bennett C, Corry P, Walsh CA, Woods CG.
Nat Genet. 2005 Apr;37(4):353-5. Epub 2005 Mar 27.
PMID 15793586
Interaction of CDK5RAP2 with EB1 to track growing microtubule tips and to regulate microtubule dynamics.
Fong KW, Hau SY, Kho YS, Jia Y, He L, Qi RZ.
Mol Biol Cell. 2009 Aug;20(16):3660-70. Epub 2009 Jun 24.
PMID 19553473
Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias.
Gotlib J, Cools J.
Leukemia. 2008 Nov;22(11):1999-2010. Epub 2008 Oct 9.
PMID 18843283
PDGFRA activating mutations in gastrointestinal stromal tumors.
Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA.
Science. 2003 Jan 31;299(5607):708-10. Epub 2003 Jan 9.
PMID 12522257
CEP215 is involved in the dynein-dependent accumulation of pericentriolar matrix proteins for spindle pole formation.
Lee S, Rhee K.
Cell Cycle. 2010 Feb;9(4):774-83. Epub 2010 Feb 9.
PMID 20139723
Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene.
Walz C, Curtis C, Schnittger S, Schultheis B, Metzgeroth G, Schoch C, Lengfelder E, Erben P, Muller MC, Haferlach T, Hochhaus A, Hehlmann R, Cross NC, Reiter A.
Genes Chromosomes Cancer. 2006 Oct;45(10):950-6.
PMID 16845659
CDK5RAP2 is required for spindle checkpoint function.
Zhang X, Liu D, Lv S, Wang H, Zhong X, Liu B, Wang B, Liao J, Li J, Pfeifer GP, Xu X.
Cell Cycle. 2009 Apr 15;8(8):1206-16. Epub 2009 Apr 16.
PMID 19282672


This paper should be referenced as such :
Huret, JL
Atlas Genet Cytogenet Oncol Haematol. 2010;14(12):1177-1178.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]


Translocations implicated (Data extracted from papers in the Atlas)

 ins(9;4)(q33;q12q25) CDK5RAP2/PDGFRA

External links

CDK5RAP2 (9q33.2) PDGFRA (4q12)

CDK5RAP2 (9q33.2) PDGFRA (4q12)

Mitelman databaseins(9;4)(q33;q12q25)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseCDK5RAP2::PDGFRA [MCList]  CDK5RAP2 (9q33.2) PDGFRA (4q12)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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