Review on ins(9;4)(q33;q12q25), with data on clinics, and the genes involved

Huret, JL

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Leukaemia Section 
Short Communication 
 
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12) 1177 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
ins(9;4)(q33;q12q25) 
Jean-Loup Huret 
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France 
(JLH) 
 
Published in Atlas Database: March 2010 
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/ins0904q33q12q25ID1450.html 
DOI: 10.4267/2042/44926 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
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 
PDGFRA 
Location 
4q25 
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). 
CDK5RAP2 
Location 
9q33 
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. 
References 
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. PDGFRA activating mutations in 
gastrointestinal stromal tumors. Science. 2003 Jan 
31;299(5607):708-10 
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, 
ins(9;4)(q33;q12q25) Huret JL 
 
 
 
 
 
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12) 1178 
Corry P, Walsh CA, Woods CG. A centrosomal mechanism 
involving CDK5RAP2 and CENPJ controls brain size. Nat 
Genet. 2005 Apr;37(4):353-5 
Walz C, Curtis C, Schnittger S, Schultheis B, Metzgeroth G, 
Schoch C, Lengfelder E, Erben P, Müller MC, Haferlach T, 
Hochhaus A, Hehlmann R, Cross NC, Reiter A. Transient 
response to imatinib in a chronic eosinophilic leukemia 
associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-
PDGFRA fusion gene. Genes Chromosomes Cancer. 2006 
Oct;45(10):950-6 
Gotlib J, Cools J. Five years since the discovery of FIP1L1-
PDGFRA: what we have learned about the fusion and other 
molecularly defined eosinophilias. Leukemia. 2008 
Nov;22(11):1999-2010 
Fong KW, Hau SY, Kho YS, Jia Y, He L, Qi RZ. Interaction of 
CDK5RAP2 with EB1 to track growing microtubule tips and to 
regulate microtubule dynamics. Mol Biol Cell. 2009 
Aug;20(16):3660-70 
Zhang X, Liu D, Lv S, Wang H, Zhong X, Liu B, Wang B, Liao 
J, Li J, Pfeifer GP, Xu X. CDK5RAP2 is required for spindle 
checkpoint function. Cell Cycle. 2009 Apr 15;8(8):1206-16 
Lee S, Rhee K. CEP215 is involved in the dynein-dependent 
accumulation of pericentriolar matrix proteins for spindle pole 
formation. Cell Cycle. 2010 Feb 15;9(4):774-83 
This article should be referenced as such: 
Huret JL. ins(9;4)(q33;q12q25). Atlas Genet Cytogenet Oncol 
Haematol. 2010; 14(12):1177-1178. 


ins(9;4)(q33;q12q25)

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