| Written | 2016-09 | Jean-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;17)(p36;q21) translocation, with data on clinics, and the genes involved. |
| Keywords | chromosome 1; chromosome 17; t(1;17)(p36;q21); PRDM16; WNT3; NSF |
| 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 | 2061 |
| Clinics and Pathology |
| Disease | Acute myeloid leukaemia. |
| Clinics | Only one case to date, a 5-year-old girl who presented with acute myeloid leukaemia. She died 6 months after diagnosis (Duhoux et al., 2012). |
| Cytogenetics |
| Cytogenetics Morphological | The t(1;17)(p36;q21) was the sole anomaly. |
| Genes involved and Proteins |
| Note | PRDM16, on chromosome 1, was implicated in the translocation. However, which gene on chromosome 17 is involved in the malignant process is unknown: two genes are located in the vicinity of the 17q21 breakpoint: WNT3 (44839872 - 44896126 bp from pter) and NSF (44668035 - 44834828 bp from pter). WNT3 (17q21.31), 355 amino acids, is one of the 19 known Wnt proteins. They bind a frizzled (Fz)/low density lipoprotein receptor related protein (LRP) complex, activating the cytoplasmic protein dishevelled ( DVL1, DVL2 or DVL3), and the b-catenin Wnt/beta catenin signaling pathway is activated (Thorstensen and Lothe, 2003). NSF (17q21.31), 744 amino acids, is a hexameric ATPase. NSF catalyzes the fusion of transport vesicles. Vesicle fusion is driven by specific associations of complementary SNARE proteins (soluble NSF attachment protein receptor) residing on the vesicle (v-SNAREs) and target (t-SNAREs) membranes. This mechanism involves NSF and its adaptor protein, NAPA. This rmechanism of vesicle fusion include endoplasmic reticulum-Golgi transport, intra-Golgi vesicle fusion, trafficking from the trans-Golgi network to the plasma membrane, neuromediator exocytosis, and synaptic vesicle fusion (Naydenov and Ivanov, 2013). |
| Gene Name | PRDM16 (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). |
| Result of the chromosomal anomaly |
| Oncogenesis | PRDM16 was not overexpressed (Duhoux et al., 2012) |
| 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 |
| 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 |
| 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 |
| NAPA (N-ethylmaleimide-sensitive factor attachment protein, alpha). |
| Naydenov NG ; Ivanov AI. |
| Atlas Genet Cytogenet Oncol Haematol. 2014;18(5):301-305. |
| The WNT signaling pathway, its role in human solid tumors. |
| Thorstensen L; Lothe RA. |
| Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):144-159. |
| Citation |
| This paper should be referenced as such : |
| Jean-Loup Huret |
| t(1;17)(p36;q21) WNT3 or NSF/PRDM16 |
| Atlas Genet Cytogenet Oncol Haematol. 2017;21(7):270-271. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0117p36q21ID2061.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(1;17)(p36;p21)WNT3/PRDM16 | |
| t(1;17)(p36;p21)NSF/PRDM16 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Nov 28 16:17:50 CET 2018 |
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