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t(4;10)(q12;q23) PDGFRA/TNKS2

Written2015-04Zachary R Chalmers, Garrett M Frampton (1), Siraj M Ali (1), Robert Ohgami(2), Curtis R Miles
Foundation Medicine, Inc. (ZRC, GMF, SMA); Stanford University School of Medicine (RO). Northwest Georgia Oncology Centers (CRM). Corresponding author: sali@foundationmedicine.com

Abstract Comprehensive genomic profiling identifies a novel PDGFRA-TNKS2 gene fusion in a female case of myeloid neoplasm with eosinophilia. The patient was treated with imatinib, and showed a dramatic and ongoing response with no evidence of disease

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9965/3 Myeloid and lymphoid neoplasms with PDGFRA rearrangement
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Atlas_Id 1468
Note This interchromosomal PDGFRA gene fusion is unlikely to be detected using surrogate CHIC2 deletion FISH testing.

Clinics and Pathology

Disease Myeloid neoplasm with eosinophilia
Epidemiology One case to date: a 58-year-old female patient (Chalmers et al., 2015).
Treatment Imatinib mesylate
Evolution Complet rmission, well tolerated response after treatment. No evidence of disease.

Genes involved and Proteins

Gene Name PDGFRA
Location 4q12
Protein Member of the type III class of tyrosine kinase receptors. Functions as homo- and/or heterodimers depending on the cell type; activated by ligand-induced dimerization and autophosphorylation. Subsequent phosphorylation of its substrates initiates a variety of signal transduction cascades that promotes cell proliferation, survival and migration through the PI3K-AKT-mTOR and RAS-MAPK pathways as well as promotes activation of STAT family members (JAK/STAT) (Zamecnikova and Bahar, 2015).
Gene Name TNKS2
Location 10q23.3
Protein Belongs to the poly(ADP-ribose)polymerase (PARP) protein super family. Role in the Wnt/beta-catenin signaling pathway. Roles of TNKS1 and TNKS2 in glucose homeostasis (Guo et al., 2012).

Result of the chromosomal anomaly

Hybrid gene
Description The hybrid gene fusion is a translocation of TNKS2 and PDGFRA with breakpoint in intron 25 and exon 12, respectively. The discovery of a novel fusion of TNKS2 with PDGFRA further demonstrates the diversity of alterations possible in these myeloid neoplasms with eosinophilia.
Detection Comprehensive genomic profiling.
  
Fusion Protein
 
  Intrachromosomal rearrangement of TNKS2 and PDGFRA. Fusion gene breakpoints are indicated by orange dashed line. ANK, ankyrin domains; ECD, extracellular domain; SAM, sterile alpha motif; TM, transmembrane; TNKS-L, tankyrase-like; TyKD, kinase domain.
  

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.

Bibliography

Comprehensive genomic profiling identifies a novel TNKS2-PDGFRA fusion that defines a myeloid neoplasm with eosinophilia that responded dramatically to imatinib therapy.
Chalmers ZR, Ali SM, Ohgami RS, Campregher PV, Frampton GM, Yelensky R, Elvin JA, Palma NA, Erlich R, Vergilio JA, Chmielecki J, Ross JS, Stephens PJ, Hermann R, Miller VA, Miles CR.
Blood Cancer J. 2015 Feb; 5(2): e278.
PMID 25658984
 
The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation.
Guo HL, Zhang C, Liu Q, Li Q, Lian G, Wu D, Li X, Zhang W, Shen Y, Ye Z, Lin SY, Lin SC.
Cell Res. 2012 Aug;22(8):1246-57.
PMID 22473005
 
PDGFRA (platelet-derived growth factor receptor, alpha polypeptide)
Zamecnikova A, Bahar S Al
Atlas Genet Cytogenet Oncol Haematol. 2015;19(3):194-197.
 

Citation

This paper should be referenced as such :
Chalmers ZR
t(4;10)(q12;q23) PDGFRA/TNKS2;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0410qq12q23ID1468.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(4;10)(q12;q23) PDGFRA/TNKS2

External links

Mitelman databaset(4;10)(q12;q23) [Case List]    t(4;10)(q12;q23) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9965/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9975/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(4;10)(q12;q23) PDGFRA/TNKS2
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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