Volume 156, Issue 1 pp. 76-88
research paper

PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Francois P. Duhoux

Francois P. Duhoux

Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain

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Geneviève Ameye

Geneviève Ameye

Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain

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Carmen P. Montano-Almendras

Carmen P. Montano-Almendras

de Duve Institute, Université catholique de Louvain, Brussels, Belgium

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Khadija Bahloula

Khadija Bahloula

Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain

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Marie J. Mozziconacci

Marie J. Mozziconacci

Institut Paoli-Calmettes, Marseilles, France

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Sophy Laibe

Sophy Laibe

Institut Paoli-Calmettes, Marseilles, France

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Iwona Wlodarska

Iwona Wlodarska

Centre for Human Genetics, K.U. Leuven, Leuven, Belgium

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Lucienne Michaux

Lucienne Michaux

Centre for Human Genetics, K.U. Leuven, Leuven, Belgium

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Pascaline Talmant

Pascaline Talmant

CHU, Nantes, France

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Steven Richebourg

Steven Richebourg

CHU, Nantes, France

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Eric Lippert

Eric Lippert

CHU, Bordeaux, France

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Frank Speleman

Frank Speleman

Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium

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Christian Herens

Christian Herens

Centre de Génétique humaine, CHU, Liège, Belgium

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Stéphanie Struski

Stéphanie Struski

Hôpital Purpan, Toulouse, France

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Sophie Raynaud

Sophie Raynaud

CHU, Nice, France

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Nathalie Auger

Nathalie Auger

Institut Gustave Roussy, Villejuif, France

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Nathalie Nadal

Nathalie Nadal

CHU Hôpital Nord, Saint-Etienne, France

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Katrina Rack

Katrina Rack

Institut de Pathologie et de Génétique, Gosselies, Belgium

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Francine Mugneret

Francine Mugneret

CHU, Dijon, France

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Isabelle Tigaud

Isabelle Tigaud

Centre Hospitalier Lyon Sud, Lyon, France

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Marina Lafage

Marina Lafage

CHU Timone, Marseilles, France

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Sylvie Taviaux

Sylvie Taviaux

Hôpital Arnaud de Villeneuve, Montpellier, France

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Catherine Roche-Lestienne

Catherine Roche-Lestienne

CHU, Lille, France

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Dominique Latinne

Dominique Latinne

Immuno-Haematology Department, Cliniques universitaires Saint- Luc, Université catholique de Louvain, Brussels, Belgium

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Jeanne M. Libouton

Jeanne M. Libouton

Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain

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Jean-Baptiste Demoulin

Jean-Baptiste Demoulin

de Duve Institute, Université catholique de Louvain, Brussels, Belgium

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Hélène A. Poirel

Hélène A. Poirel

Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain

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on behalf of the Groupe Francophone de Cytogénétique Hématologique (GFCH) and of the Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO)

on behalf of the Groupe Francophone de Cytogénétique Hématologique (GFCH) and of the Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO)

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First published: 03 November 2011
Citations: 46
Hélène A Poirel, Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Avenue Mounier 10F, 1200 Brussels, Belgium.
E-mail: [email protected]

Summary

The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34+ cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.

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