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

2016-09-01   Jean-Loup Huret 

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


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

Clinics and Pathology

Phenotype stem cell origin

Only one case to date (Masetti et al 2014).


CLINICS An 8-year-old child was diagnosed with acute monoblastic leukemia with differentiation (AML-M5b).


5 years after the allograft, the patient was alive and disease-free.

Genes Involved and Proteins

Gene name
PRDM16 (PR domain containing 16)
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
SKI (SKI proto-oncogene)
Protein description
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


5 PRDM16 ? 3 SKI; breakpoint: AAG CTA GCC AAA A - GT CTC CTC TGAFusion of PRDM16 exon 1 (MRSKARARKLAK) to SKI exon 2 (VSSEPPASIRPK.)

Highly cited references

Pubmed IDYearTitleCitations
246736272014Whole transcriptome sequencing of a paediatric case of de novo acute myeloid leukaemia with del(5q) reveals RUNX1-USP42 and PRDM16-SKI fusion transcripts.4
338368352021Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns.1


Pubmed IDLast YearTitleAuthors
246736272014Whole 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 et al
256702022015Ski regulates Hippo and TAZ signaling to suppress breast cancer progression.Rashidian J et al
247367332015The SMAD-binding domain of SKI: a hotspot for de novo mutations causing Shprintzen-Goldberg syndrome.Schepers D et al
244156292014The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease.Singbrant S et al
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
196414922009Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.Kajimura S et al


Fusion gene



Jean-Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2016-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1642/t(1;1)(p36;p36)