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

2015-04-01   Zachary R Chalmers , Garrett M Frampton (1) , Siraj M Ali (1) , Robert Ohgami(2) , Curtis R Miles 

1.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

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 (platelet-derived growth factor receptor, alpha polypeptide)
Location
4q12
Protein description
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 (tankyrase 2)
Location
10q23.32
Protein description
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

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 protocole

Comprehensive genomic profiling.
Atlas Image
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.

Bibliography

Pubmed IDLast YearTitleAuthors
256589842015Comprehensive genomic profiling identifies a novel TNKS2-PDGFRA fusion that defines a myeloid neoplasm with eosinophilia that responded dramatically to imatinib therapy.Chalmers ZR et al
224730052012The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation.Guo HL et al

Summary

Note

This interchromosomal PDGFRA gene fusion is unlikely to be detected using surrogate CHIC2 deletion FISH testing.

Citation

Zachary R Chalmers ; Garrett M Frampton (1) ; Siraj M Ali (1) ; Robert Ohgami(2) ; Curtis R Miles

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

Atlas Genet Cytogenet Oncol Haematol. 2015-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1468/t(4;10)(q12;q23)

External Links