t(5;15)(q33;q22) TP53BP1/PDGFRB

2006-02-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH); Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, PR China (YX)

Clinics and Pathology

Disease

Atypical chronic myelogenous leukemia (a-CML) (BCR-ABL negative chronic myeloproliferative disease)

Epidemiology

Only one case to date, a 79 yr old male patient

Prognosis

The disease was sensitive to imatinib, but the patient developped resistance to imatinib and died 14 mths after diagnosis

Genes Involved and Proteins

Gene name
PDGFRB (platelet-derived growth factor receptor, beta polypeptide)
Location
5q32
Protein description
PDGFRB is the receptor for PDGFB (platelet-derived growth factor-b); Ig like, transmembrane and tyrosine kinase domains; membrane tyrosine kinase; can homodimerize
Gene name
TP53BP1 (tumor protein p53 binding protein 1)
Location
15q15.3
Protein description
Component of the cellular response to DNA damage

Result of the Chromosomal Anomaly

Description

5 TP53BP1-3 PDGFRB; breakpoint in PDGFRB intron 10, identical to most PDGFRB breakpoints; exon 23 of TP53BP1 fused in frame to PDGFRB exon 11; reciprocal product not detectable247 kDa; composed of the N-term TP53BP1 including the coiled coil domains and the kinetochore binding domain from TP53BP1 fused to the transmembrane and the tyrosine kinase domains of PDGFRB C-term.

Oncogenesis

The coiled coil domains from TP53BP1 may mediate PDGFRB homodimerization and constitutive activation of its tyrosine kinase activity; on the other hand, the DNA damage response of TP53BP1 may be perturbed.

Highly cited references

Pubmed IDYearTitleCitations
154922362004p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder.9
221693002011[Application of reverse transcription-multiplex nested PCR to detect PDGFRB gene rearrangement in myeloproliferative disorders].0

Bibliography

Pubmed IDLast YearTitleAuthors
153417212004The Tudor tandem of 53BP1: a new structural motif involved in DNA and RG-rich peptide binding.Charier G et al
154922362004p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder.Grand FH et al
113313102001Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways.Rappold I et al
16260621200553BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice.Ward IM et al
160241192005ATM signaling and 53BP1.Zgheib O et al

Summary

Fusion gene

TP53BP1/PDGFRB TP53BP1 (15q15.3) PDGFRB (5q32) M t(5;15)(q32;q15)|TP53BP1/PDGFRB TP53BP1 (15q15.3) PDGFRB (5q32) TIC

Citation

Jean-Loup Huret

t(5;15)(q33;q22) TP53BP1/PDGFRB

Atlas Genet Cytogenet Oncol Haematol. 2006-02-01

Online version: http://atlasgeneticsoncology.org/haematological/1326/t(5;15)(q33;q22)

External Links