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

2010-03-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


One case to date, a 71-year-old female patient with chronic eosinophilic leukemia in accelerated phase (Walz et al., 2006)..


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 name
PDGFRA (platelet-derived growth factor receptor, alpha polypeptide)
Protein description
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 name
CDK5RAP2 (CDK5 regulatory subunit associated protein 2)
Protein description
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


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.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.


Constitutive tyrosine kinase activity is likely.

Highly cited references

Pubmed IDYearTitleCitations
168456592006Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene.14


Pubmed IDLast YearTitleAuthors
157935862005A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size.Bond J et al
195534732009Interaction of CDK5RAP2 with EB1 to track growing microtubule tips and to regulate microtubule dynamics.Fong KW et al
188432832008Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias.Gotlib J et al
125222572003PDGFRA activating mutations in gastrointestinal stromal tumors.Heinrich MC et al
201397232010CEP215 is involved in the dynein-dependent accumulation of pericentriolar matrix proteins for spindle pole formation.Lee S et al
168456592006Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene.Walz C et al
192826722009CDK5RAP2 is required for spindle checkpoint function.Zhang X et al


Fusion gene

CDK5RAP2/PDGFRA CDK5RAP2 (9q33.2) PDGFRA (4q12) M ins(9;4)(q33;q12q25)|CDK5RAP2/PDGFRA CDK5RAP2 (9q33.2) PDGFRA (4q12) TIC


Jean-Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2010-03-01

Online version:;4)(q33;q12q25)-cdk5rap2-pdgfra

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