t(1;1)(p36;q41) DUSP10/PRDM16

2016-07-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr

Abstract

Review on t(1;1)(p36;q41) DUSP10/PRDM16 translocations, with data on clinics, and the genes involved.

Clinics and Pathology

Disease

Acute myeloid leukemia.

Clinics

CLINICS A 25-year-old male patient presented acute monoblastic leukemia without differentiation (FAB type M5a) (Noguchi et al 2007).).

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
DUSP10 (dual specificity phosphatase 10)
Location
1q41
Protein description
482 amino acids. DUSP10 is a MAP kinase phosphatase. DUSP10 inactivate p38MAPK signaling by dephosphorylation. Activation/phosphorylation of the p38MAPK pathway inhibits tumor formation (the p38MAPK subfamily is composed by four members: MAPK11, MAPK12, MAPK13 and MAPK14 ). DUSP10 mRNA levels were lower in prostate cell lines derived from malignant tumor (Nonn L, 2011). High DUSP10 expression in colorectal cancer was found associated with improvement in survival. DUSP10 negatively regulates intestinal epithelial cell growth and acts as a suppressor for colorectal cancer (Png et al., 2016). DUSP10 polymorphisms influence the risk of developing colorectal cancer. DUSP10 was found expressed in meningiomas of all grades. DUSP10 expression with deactivation of p38MAPK may contribute to the pathogenesis of meningiomas (Johnson et al., 2016). AGR2, a protein known to be overexpressed in various human cancers and to provide a poor prognosis, up-regulates DUSP10 which subsequently inhibits p38MAPK, prevents TP53 activation by phosphorylation, and provides a poor prognosis in ER+breast cancer (Hrstka et al., 2016). mTORC2 (MTOR protein complex 2) binds and phosphorylates DUSP10, which blocks DUSP10 turnover resulting in inactivation of p38MAPK signaling. DUSP10 protein levels and phosphorylation is increased inglioblastoma multiforme tumors (Benavides-Serrato et al., 2014). MIR92A/DUSP10/JNK signaling: MIR92A targets DUSP10 (DUSP10 inhibits JKN signaling (MAPK8, MAPK9 and MAPK10, also called JNK1,2,3) to promote JNK signaling, which promotes pancreatic cancer cell proliferation. (He et al., 2014).

Result of the Chromosomal Anomaly

Description

5 DUSP10 - 3 PRDM16. The splice junction was in intron 1 of DUSP10 and in exon 4 of PRDM16.The breakpoint within PRDM16 induced the disruption of the PRDI-BF1-RIZ1 homologous (PR) domain.

Bibliography

Pubmed IDLast YearTitleAuthors
213436122011Prdm16 is a physiologic regulator of hematopoietic stem cells.Aguilo F et al
255686652014mTORC2 modulates feedback regulation of p38 MAPK activity via DUSP10/MKP5 to confer differential responses to PP242 in glioblastoma.Benavides-Serrato A 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
243326502014miR-92a/DUSP10/JNK signalling axis promotes human pancreatic cancer cells proliferation.He G et al
267332322016AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10-mediated regulatory pathway.Hrstka R et al
270509152016p38MAPK activation and DUSP10 expression in meningiomas.Johnson MD et al
196414922009Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.Kajimura S et al
173219992007Dual-specificity phosphatase 10 is fused to MDS1/EVI1-like gene 1 in a case of acute myelogenous leukemia with der1t1;1(p36.3;q21).Noguchi M et al
257722342016DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis.Png CW et al

Summary

Fusion gene

DUSP10/PRDM16

Citation

Jean-Loup Huret

t(1;1)(p36;q41) DUSP10/PRDM16

Atlas Genet Cytogenet Oncol Haematol. 2016-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1645/t(1;1)(p36;q41)

External Links