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

Written2016-07Jean-Loup Huret
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.

Keywords chromosome 1; t(1;1)(p36;q41); PRDM16; DUSP10

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1645

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).).

Cytogenetics

Cytogenetics Morphological The der(1)t(1;1)(p36.3;q41) was the sole abnormality.

Genes involved and Proteins

Gene NamePRDM16 (PR domain containing 16)
Location 1p36.32
Dna / Rna 11 splice variants
Protein 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 NameDUSP10 (dual specificity phosphatase 10)
Location 1q41
Protein 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

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

Prdm16 is a physiologic regulator of hematopoietic stem cells.
Aguilo F, Avagyan S, Labar A, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY, Snoeck HW.
Blood. 2011 May 12;117(19):5057-66. doi: 10.1182/blood-2010-08-300145. Epub 2011 Feb 22.
PMID 21343612
 
mTORC2 modulates feedback regulation of p38 MAPK activity via DUSP10/MKP5 to confer differential responses to PP242 in glioblastoma.
Benavides-Serrato A, Anderson L, Holmes B, Cloninger C, Artinian N, Bashir T, Gera J.
Genes Cancer. 2014 Nov;5(11-12):393-406.
PMID 25568665
 
Prdm16 is required for normal palatogenesis in mice.
Bjork BC, Turbe-Doan A, Prysak M, Herron BJ, Beier DR.
Hum Mol Genet. 2010 Mar 1;19(5):774-89. doi: 10.1093/hmg/ddp543. Epub 2009 Dec 11.
PMID 20007998
 
The Multifaceted Roles of PRDM16: Adipose Biology and Beyond.
Chi J, Cohen P.
Trends Endocrinol Metab. 2016 Jan;27(1):11-23. doi: 10.1016/j.tem.2015.11.005. Epub 2015 Dec 11. Review.
PMID 26688472
 
Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.
Chuikov S, Levi BP, Smith ML, Morrison SJ.
Nat Cell Biol. 2010 Oct;12(10):999-1006. doi: 10.1038/ncb2101. Epub 2010 Sep 12.
PMID 20835244
 
PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
Duhoux FP, Ameye G, Montano-Almendras CP, Bahloula K, Mozziconacci MJ, Laibe S, Wlodarska I, Michaux L, Talmant P, Richebourg S, Lippert E, Speleman F, Herens C, Struski S, Raynaud S, Auger N, Nadal N, Rack K, Mugneret F, Tigaud I, Lafage M, Taviaux S, Roche-Lestienne C, Latinne D, Libouton JM, Demoulin JB, Poirel HA; Groupe Francophone de Cytogénétique Hématologique (GFCH); Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO).
Br J Haematol. 2012 Jan;156(1):76-88. doi: 10.1111/j.1365-2141.2011.08918.x. Epub 2011 Nov 3.
PMID 22050763
 
miR-92a/DUSP10/JNK signalling axis promotes human pancreatic cancer cells proliferation.
He G, Zhang L, Li Q, Yang L.
Biomed Pharmacother. 2014 Feb;68(1):25-30. doi: 10.1016/j.biopha.2013.11.004. Epub 2013 Nov 26.
PMID 24332650
 
AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10-mediated regulatory pathway.
Hrstka R, Bouchalova P, Michalova E, Matoulkova E, Muller P, Coates PJ, Vojtesek B.
Mol Oncol. 2016 May;10(5):652-62. doi: 10.1016/j.molonc.2015.12.003. Epub 2015 Dec 17.
PMID 26733232
 
p38MAPK activation and DUSP10 expression in meningiomas.
Johnson MD, Reeder JE, O'Connell M.
J Clin Neurosci. 2016 Aug;30:110-4. doi: 10.1016/j.jocn.2015.12.031. Epub 2016 Apr 3.
PMID 27050915
 
Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.
Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM.
Nature. 2009 Aug 27;460(7259):1154-8. Epub 2009 Jul 29.
PMID 19641492
 
Dual-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, Tashiro H, Shirasaki R, Gotoh M, Kawasugi K, Shirafuji N.
Int J Hematol. 2007 Feb;85(2):175-6. No abstract available.
PMID 17321999
 
DUSP10 (dual specificity phosphatase 10)
Nonn, L
Atlas Genet Cytogenet Oncol Haematol. 2011;15(2):148-149.
 
DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis.
Png CW, Weerasooriya M, Guo J, James SJ, Poh HM, Osato M, Flavell RA, Dong C, Yang H, Zhang Y.
Oncogene. 2016 Jan 14;35(2):206-17. doi: 10.1038/onc.2015.74. Epub 2015 Mar 16.
PMID 25772234
 

Citation

This paper should be referenced as such :
Huret JL
t(1;1)(p36;q41) DUSP10/PRDM16;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0101q41ID1645.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(1;1)(p36;q41) DUSP10/PRDM16

External links

Mitelman databaset(1;1)(p36;q41) [Case List]    t(1;1)(p36;q41) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(1;1)(p36;q41) DUSP10/PRDM16
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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