t(4;12)(q12;p13) PDGFRA/ETV6
2008-04-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Disease
Myeloproliferative disease with eosinophilia
Epidemiology
Only one case to date, a 51 year old male patient.
Evolution
The disease was rather indolent for over 7 years; imatinib was then started with significant resolution of symptoms, and the patient remains in cytogenetic remission 9 months later.
Genes Involved and Proteins
Gene name
PDGFRA (platelet-derived growth factor receptor, alpha polypeptide)
Location
4q12
Protein description
Composed of an extracellular domain (the immunoglobulin-like motifs), a transmembrane domain, with an inhibitory juxtamembrane WW-like domain (Irusta et al., 2002), and an intracellular domain (kinase domain); receptor tyrosine kinase; forms homodimer, and heterodimer with PDGFRB; dimerization induces kinase domain activation, leading to the activation of intracellular signalling pathways (Kawagishi et al., 1995).
Somatic mutations
Hybrid genes between various partners and PDFRGA occur in chronic myeloid leukaemia-like diseases with eosinophilia, mostly chronic eosinophilic leukemia (CEL), a clonal hypereosinophilic syndrome. PDGFRA partners known so far are: STRN (2p24) (Curtis et al., 2007), FIP1L1 (4q12) (Cools et al., 2003, Pardanani et al., 2004), CDK5RAP2 (9q33) (Walz et al., 2006), KIF5B (10p11) (Score et al., 2006), ETV6 (12p13), herein described (Curtis et al., 2007), and BCR (22q11) (Baxter et al., 2002).
Mutations of platelet-derived growth factor receptor-alpha (PDGFRA) are observed in a subset of gastrointestinal stromal tumors (GISTs) (Heinrich et al., 2003).
Tumours with PDGFRA involvement are responsive to imatinib therapy (Cools et al., 2003; Debiec-Rychter et al., 2004).
Mutations of platelet-derived growth factor receptor-alpha (PDGFRA) are observed in a subset of gastrointestinal stromal tumors (GISTs) (Heinrich et al., 2003).
Tumours with PDGFRA involvement are responsive to imatinib therapy (Cools et al., 2003; Debiec-Rychter et al., 2004).
Gene name
ETV6 (ets variant 6)
Location
12p13.2
Protein description
Contains a HLH domain and a ETS-DNA binding domain; ETS-related transcription regulator.
Result of the Chromosomal Anomaly
Transcript
5 ETV6-3 PDGFRA; Fusion between ETV6 intron 6 and PDGFRA intron 11; reciprocal product not found -> in frame fusion between ETV6 exon 6 and PDGFRA exon 12.
Description
The N-term ETV6- C-term PDGFRA fusion protein retains most of ETV6, including the pointed domain and the ETS domain, fused to the WW-like domain and the kinase domain of PDGFRA; altough the WW-like domain is thought to act as an autoinhibitory element preventing kinase over-activation.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 29541391 | 2018 | Acute myeloid leukemia with t(4;12)(q12;p13): an aggressive disease with frequent involvement of PDGFRA and ETV6. | 25 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
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Summary
Note
See also the t(4;12)(q11-q21;p13) with CHIC2.and ETV6 involvements in M0 acute myeloid leukaemia (M0-AML), keeping in mind that a t(4:12)(q13-21;p12-13) has also been described in B-cell acute lymphocytic leukaemia (ALL) (GFCH, 1993; Behm et al., 1996; Elghezal et al., 2001), B-cell non Hodgkins lymphoma (NHL) (Schouten et al., 1990; Palanisamy et al., 2002), and in a case of adult T-cell lymphoma/leukemia (Sadamori et al., 1991).
Citation
Jean-Loup Huret
t(4;12)(q12;p13) PDGFRA/ETV6
Atlas Genet Cytogenet Oncol Haematol. 2008-04-01
Online version: http://atlasgeneticsoncology.org/haematological/2137/t(4;12)(q12;p13)-pdgfra-etv6
