PRDM16 (PR domain containing 16), SPOP (speckle type BTB/POZ protein), ">

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Nervous system: Astrocytoma with t(1;17)(p36;q21) SPOP/PRDM16

Written2016-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr

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Abstract

Abstract Review on t(1;17)(p36;q21) SPOP/PRDM16 translocation in astrocytic tumor, with data on the genes involved.

Identity

ICD-Topo C710-C714,C717-C719,C720-C725,C716
ICD-Morpho 9400/3
Atlas_Id 5447
Phylum Nervous system: Central Nervous system::Astrocytic tumor

Clinics and Pathology

Disease A t(1;17)(p36;q21) was found in a case of astrocytoma grade I-II, but no further data is available (Yoshihara et al 2015).
Phenotype / cell stem origin EMBRYONIC_ORIGIN
Clinics Grade I astrocytomas are pilocytic astrocytoma and subependymal giant cell astrocytoma, the latter being the most common central nervous system neoplasm in tuberous sclerosis; they are slow growing tumors; they typically occur during the first two decades of life. Grade II astrocytomas are pilomyxoid astrocytoma occurring most often in infants and very young children, diffuse astrocytoma, seen at any age, but often between ages 30-40, and pleomorphic xanthoastrocytoma, typically developing in children and young adults.

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 NameSPOP (speckle type BTB/POZ protein)
Location 17q21.33
Dna / Rna 24 splice variants
Protein 374 amino acids SPOP comprises a N-term MATH domain (Meprin And TRAF Homology; substrate recognition and binding), a BTB/POZ domain (Bric-a-brac, Tramtrack and Broad complex/ Pox virus and Zinc finger; connects to the CUL3 - RBX1 (Cullin 3-RING box 1) scaffold protein), a 3-box domain (facilitating CUL3 binding and resembling to F-/SOCS-boxes) and a C-terminal nuclear localization sequence. SPOP is a E3 ubiquitin ligase adaptor protein that participates in the degradation of various substrates. AR (androgen receptor), DAXX, BMI1, BRMS1 and PDX1 are targets of SPOP. SPOP is critically involved in SETD2 (a tumor suppressor) stability. SPOP enables homology-directed DNA repair of double strand breaks, and mutant SPOP promotes genomic rearrangements within chromosomes. SPOP suppresses gastric tumorigenesis through inhibiting hedgehog/ GLI2 signaling pathway. SPOP is frequently mutated in prostate and endometrial cancers. TMPRSS2 - ERG fusions, frequently seen in prostate carcinoma, encode N-terminal-truncated ERG proteins that are resistant to the SPOP-mediated degradation. Decreased expression of SPOP is associated with poor prognosis in glioma. On the other hand, SPOP is highly expressed in clear cell renal cell carcinoma (Zhuang et al., 2009; Mani, 2014; Zeng et al., 2014; Karnes et al., 2015; Ding et al., 2015; Rider and Cramer, 2015).

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
 
Truncated ERG Oncoproteins from TMPRSS2-ERG Fusions Are Resistant to SPOP-Mediated Proteasome Degradation.
An J, Ren S, Murphy SJ, Dalangood S, Chang C, Pang X, Cui Y, Wang L, Pan Y, Zhang X, Zhu Y, Wang C, Halling GC, Cheng L, Sukov WR, Karnes RJ, Vasmatzis G, Zhang Q, Zhang J, Cheville JC, Yan J, Sun Y, Huang H.
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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.
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Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.
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PMID 20835244
 
Decreased expression of the SPOP gene is associated with poor prognosis in glioma.
Ding D, Song T, Jun W, Tan Z, Fang J.
Int J Oncol. 2015 Jan;46(1):333-41. doi: 10.3892/ijo.2014.2729. Epub 2014 Oct 24.
PMID 25351530
 
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PMID 19641492
 
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Mani RS.
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SPOP suppresses tumorigenesis by regulating Hedgehog/Gli2 signaling pathway in gastric cancer.
Zeng C, Wang Y, Lu Q, Chen J, Zhang J, Liu T, Lv N, Luo S.
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PMID 25204354
 
Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.
Zhuang M, Calabrese MF, Liu J, Waddell MB, Nourse A, Hammel M, Miller DJ, Walden H, Duda DM, Seyedin SN, Hoggard T, Harper JW, White KP, Schulman BA.
Mol Cell. 2009 Oct 9;36(1):39-50. doi: 10.1016/j.molcel.2009.09.022.
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Citation

This paper should be referenced as such :
Huret JL
Nervous system: Astrocytoma with t(1;17)(p36;q21) SPOP/PRDM1
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Tumors/t0117p36q21ID5447.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(1;17)(p36;q21) SPOP/PRDM16

External links

Mitelman database t(1;17)(p36;q21) SPOP/PRDM16 [Case List]    t(1;17)(p36;q21) SPOP/PRDM16 [Association List] Mitelman database (CGAP - NCBI)
arrayMap arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaseNervous system: Astrocytoma with t(1;17)(p36;q21) SPOP/PRDM16
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed


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