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t(1;1)(p36;p36) PRDM16::SKI

Written2016-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France.

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

Keywords chromosome 1; t(1;1)(p36;p36), SKI; PRDM16

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1642

Clinics and Pathology

Disease Acute myeloid leukemia (AML)
Phenotype / cell stem origin Only one case to date (Masetti et al 2014).
Clinics CLINICS An 8-year-old child was diagnosed with acute monoblastic leukemia with differentiation (AML-M5b).
Prognosis 5 years after the allograft, the patient was alive and disease-free.


Additional anomalies The patient also had a t(7;21)(p22;q22) RUNX1 / USP42, and a del(5)(q14q34)

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 NameSKI (SKI proto-oncogene)
Location 1p36.33
Protein Negative regulator of the TGFB)/Smad signaling. SKI and SKIL (SnoN) are transcriptional co-repressors which interact with Smads, and repress transcription induced by TGFB. TGFB signaling suppresses tumor cell proliferation at early stages of tumorigenesis but promotes epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastasis at late malignant stages. SKI interacts with the Hippo pathway. SKI inhibites the transcription activity of TAZ as well as its ability to promote transformation and EMT (Rashidian et al., 2015). High expression of SKI results in activation of hematopoietic stem cells transcriptional programs and an HSC autonomous repopulating advantage that favors myeloid development through hepatocyte growth factor (HGF) signaling and independently of its ability to inhibit TGFB signaling. SKI is highly expressed in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) (Singbrant et al., 2014). SKI has a critical role in the development of neuronal and muscle cells or tissues. SKI mutations have been identified in Shprintzen-Goldberg syndrome (SGS) (Schepers et al., 2015).

Result of the chromosomal anomaly

Hybrid gene
Description 5' PRDM16 ? 3' SKI; breakpoint: AAG CTA GCC AAA A - GT CTC CTC TGA
Fusion Protein
Description Fusion of PRDM16 exon 1 (MRSKARARKLAK) to SKI exon 2 (VSSEPPASIRPK.)

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.


Whole transcriptome sequencing of a paediatric case of de novo acute myeloid leukaemia with del(5q) reveals RUNX1-USP42 and PRDM16-SKI fusion transcripts.
Masetti R, Togni M, Astolfi A, Pigazzi M, Indio V, Rivalta B, Manara E, Rutella S, Basso G, Pession A, Locatelli F.
Br J Haematol. 2014 Aug;166(3):449-52. doi: 10.1111/bjh.12855. Epub 2014 Mar 27. Review. No abstract available.
PMID 24673627
Ski regulates Hippo and TAZ signaling to suppress breast cancer progression.
Rashidian J, Le Scolan E, Ji X, Zhu Q, Mulvihill MM, Nomura D, Luo K.
Sci Signal. 2015 Feb 10;8(363):ra14. doi: 10.1126/scisignal.2005735.
PMID 25670202
The SMAD-binding domain of SKI: a hotspot for de novo mutations causing Shprintzen-Goldberg syndrome.
Schepers D, Doyle AJ, Oswald G, Sparks E, Myers L, Willems PJ, Mansour S, Simpson MA, Frysira H, Maat-Kievit A, Van Minkelen R, Hoogeboom JM, Mortier GR, Titheradge H, Brueton L, Starr L, Stark Z, Ockeloen C, Lourenco CM, Blair E, Hobson E, Hurst J, Maystadt I, Destrée A, Girisha KM, Miller M, Dietz HC, Loeys B, Van Laer L.
Eur J Hum Genet. 2015 Feb;23(2):224-8. doi: 10.1038/ejhg.2014.61. Epub 2014 Apr 16.
PMID 24736733
The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease.
Singbrant S, Wall M, Moody J, Karlsson G, Chalk AM, Liddicoat B, Russell MR, Walkley CR, Karlsson S.
Haematologica. 2014 Apr;99(4):647-55. doi: 10.3324/haematol.2013.093971. Epub 2014 Jan 10.
PMID 24415629
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
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
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


This paper should be referenced as such :
Jean-Loup Huret
t(1;1)(p36;p36) PRDM16/SKI
Atlas Genet Cytogenet Oncol Haematol. 2017;21(6):218-219.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes SKI

Translocations implicated (Data extracted from papers in the Atlas)

 t(1;1)(p36;p36) PRDM16/SKI

External links

Mitelman databaset(1;1)(p36;p36)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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