t(1;12)(p36;p13) ETV6/PRDM16

2016-08-01   Francois P. Duhoux , Hélène A. Poirel 

1.Cliniques universitaires Saint-Luc, Université catholique de Louvain / helene.antoine-poirel@uclouvain.be
2.Cliniques universitaires Saint-Luc, Université catholique de Louvain / helene.antoine-poirel@uclouvain.be

Abstract

Review on t(1;12)(p36;p13) translocations, with data on clinics, and the genes involved.

Clinics and Pathology

Phenotype stem cell origin

AML M4 according to immunophenotyping vs M1 according to cytology.

Epidemiology

Found in one case of AML in a 46 years old female Duhoux et al., 2012).

Clinics

(

Cytology

Leukemic infiltrate of myeloid origin (blasts I and II); high proportion of myeloid blast cells and restricted percentage of monocytes.

Prognosis

The patient died 12 months after diagnosis.

Cytogenetics

Cytogenetics morphological

The t(1;12)(p36;p13.2) was the sole anomaly.
Atlas Image
Atlas Image
Left: FISH using the LSI® ETV6 probe : the probe is split between the der(1) and the der(12. Right: FISH using specific probes for PRDM16 (RP5-907A6 and RP1-163G9): the RP1-163G9 probe is split between the der(1) and the der(12), the RP5-907A6 probe is translocated to the der(12)PROBES RP5-907A6 (FITC), RP1-163G9 (Cy3) and LSI® ETV6

Genes Involved and Proteins

Gene name
PRDM16 (PR domain containing 16)
Location
1p36.32
Dna rna description
11 splice variants
Protein description
1276 amino acids and smaller proteins. Contains a N-term PR domain; 7 Zinc fingers, a proline-rich domain, and 3 Zinc fingers in the C-term. Binds DNA. Transcription activator; PRDM16 has an intrinsic histone methyltransferase activity. PRDM16 forms a transcriptional complex with CEBPB. PRDM16 plays a downstream regulatory role in mediating TGFB signaling (Bjork et al., 2010). PRDM16 induces brown fat determination and differentiation. PRDM16 is expressed selectively in the earliest stem and progenitor hematopoietic cells, and is required for the maintenance of the hematopoietic stem cell pool during development. PRDM16 is also required for survival, cell-cycle regulation and self-renewal in neural stem cells (Chuikov et al., 2010; Kajimura et al., 2010; Aguilo et al., 2011; Chi and Cohen, 2016).
Gene name
ETV6 (ets variant 6)
Location
12p13.2
Protein description
452 amino acids. The ETV6 protein contains from N-term to C-Term a HLH (helix-loop-helix, aa 40-124) domain (also referred to as the pointed or sterile alpha motif domain), responsible for hetero- and homodimerization, an internal domain, involved in the recruitment of a repression complex including NCOR1 (17p12), NCOR2 (12q24.31), SIN3A (15q24.2), and SIN3B (19p13.11), and an ETS domain (aa 339-420), responsible for sequence specific DNA-binding and protein-protein interaction (De Braekeleer et al., 2014).

Result of the Chromosomal Anomaly

Atlas Image
Schematic representation of the putative ETV6-PRDM16 fusion protein, PRD = prolin-rich domain, DBD1 = DNA-binding domain 1, PRR = prolin-rich domain, RD = repressor domain, DBD2 = DNA-binding domain 2, AD = acidic domain.

Description

ETV6 exon 4 is fused to PRDM16 exon 2.

Detection protocole

PCR, FISH.

Bibliography

Pubmed IDLast YearTitleAuthors
213436122011Prdm16 is a physiologic regulator of hematopoietic stem cells.Aguilo F et al
200079982010Prdm16 is required for normal palatogenesis in mice.Bjork BC et al
266884722016The Multifaceted Roles of PRDM16: Adipose Biology and Beyond.Chi J et al
208352442010Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.Chuikov S et al
220507632012PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.Duhoux FP et al
196414922009Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.Kajimura S et al

Summary

Fusion gene

ETV6/PRDM16

Citation

Francois P. Duhoux ; Hélène A. Poirel

t(1;12)(p36;p13) ETV6/PRDM16

Atlas Genet Cytogenet Oncol Haematol. 2016-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1697/t(1;12)(p36;p13)

External Links