t(1;3)(p36;q21) RPN1/PRDM16

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;3)(p36;q21) translocations, with data on clinics, and the genes involved.

Clinics and Pathology


Myelodysplastic syndromes and acute myeloid leukaemias


A t(1;3)(p36;q21) RPN1/PRDM16 was found in 35 cases (Mochizuki et al., 2000; Shimizu et al., 2000: Xinh et al., 2003; Duhoux et al., 2012)

Phenotype stem cell origin

There were 19 myeloproliferative/myelodysplastic syndromes: 1 chronic myeloid leukemia (CML), 3 refractory anaemia with ring sideroblasts (RARS); 6 refractory anemia with excess blasts (RAEB, RAEB2, RAEB-T), 6 chronic myelomonocytic leukaemia (CMML) and 3 myelodysplastic syndrome not otherwise specified (MDS-NOS); and 16, acute myeloid leukaemias; 7 apparently de novo (AML- M1, M2, M4, M5a, M6 and NOS), and 9 therapy-related or secondary AML.


Median age was 66 years (range 29-92). Sex ratio was 21 male/14 female patients (3/5 male, 2/5 female).
Atlas Image
Survival in 29 patients with t(1;3)(p36;q21) RPN1/PRDM16


Median survival in 29 patients was 13-15 months; five patients died within a month after diagnosis, while 2 patients were long survivors (65 months + and 80 months+).

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
RPN1 (ribophorin I)
RPN1 (Ribophorin I) (3q21.3, starts at 128338813 and ends at 128369719 bp from pter) must not be confused with PSMD2 (proteasome 26S subunit, non-ATPase 2) (3q27.1; starts at 184018369 and ends at 184026842 bp from pter). PSMD2 aliases are: RPN1, P97, S2, TRAP2 (see above).
Dna rna description
8 splice variants
Protein description
607 amino acids. RPN1 comprised of a signal peptide (aa 1-23).RPN1 (Ribophorin I) is an endoplasmic reticulum transmembrane protein and a subunit of the oligosaccharyltransferase (OST) complex. RPN1 regulates the delivery of precursor proteins to the OST complex by presenting them to the catalytic core. RPN1 acts as a substrate-specific facilitator of N-glycosylation It may function as a chaperone that recognizes misfolded proteins, and plays a role in protein quality control in association with MLEC (malectin) (Wilson and High, 2007; Wilson et al., 2008; Takeda et al., 2014).

Result of the Chromosomal Anomaly


5 RPN1 translocated to 3 PRDM16. The breakpoint in PRDM16 is located either in the ?rst intron, or 5 of exon 1. Transcriptional activation of can occur in some patients, and fusion transcripts have been generated in other patients.


The 5 flanking regions of the rat RPN1 gene containes GC-rich elements and an octamer motif. It could serve as an enhancer, to activate transcription of PRDM16 (Mochizuki et al., 2000; Shimizu et al., 2000). Overexpression of PRDM16 (Duhoux et al., 2012).


Pubmed IDLast YearTitleAuthors
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
220507632012PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.Duhoux FP et al
196414922009Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.Kajimura S et al
110500052000A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells.Mochizuki N et al
106799112000Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).Shimizu S et al
254512652014Association of malectin with ribophorin I is crucial for attenuation of misfolded glycoprotein secretion.Takeda K et al
172641542007Ribophorin I acts as a substrate-specific facilitator of N-glycosylation.Wilson CM et al
186070032008Ribophorin I regulates substrate delivery to the oligosaccharyltransferase core.Wilson CM et al
125572312003Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1.Xinh PT et al


Fusion gene



A translocation t(1;3)(p36;q21), with the same breakpoints but involving PSMD2 and PRDM16 probably does not exist:
1- PSMD2 sits in 3q27, while the breakpoint is in 3q21;
2- PSMD2, a protein of the proteasome, is mainly known in PubMed by its alias: "RPN1", while the true RPN1, a protein involved in N-glycosylation and sitting in 3q21, is better known by its full name: "Ribophorin I".
Hence the confusion, found in a number of papers of the literature.


Jean-Loup Huret

t(1;3)(p36;q21) RPN1/PRDM16

Atlas Genet Cytogenet Oncol Haematol. 2016-09-01

Online version: http://atlasgeneticsoncology.org/haematological/2048/t(1;3)(p36;q21)