PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies
Francois P. Duhoux
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorGeneviève Ameye
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorCarmen P. Montano-Almendras
de Duve Institute, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorKhadija Bahloula
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorMarie J. Mozziconacci
Institut Paoli-Calmettes, Marseilles, France
Search for more papers by this authorIwona Wlodarska
Centre for Human Genetics, K.U. Leuven, Leuven, Belgium
Search for more papers by this authorLucienne Michaux
Centre for Human Genetics, K.U. Leuven, Leuven, Belgium
Search for more papers by this authorFrank Speleman
Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorChristian Herens
Centre de Génétique humaine, CHU, Liège, Belgium
Search for more papers by this authorKatrina Rack
Institut de Pathologie et de Génétique, Gosselies, Belgium
Search for more papers by this authorSylvie Taviaux
Hôpital Arnaud de Villeneuve, Montpellier, France
Search for more papers by this authorDominique Latinne
Immuno-Haematology Department, Cliniques universitaires Saint- Luc, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorJeanne M. Libouton
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorJean-Baptiste Demoulin
de Duve Institute, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorHélène A. Poirel
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authoron behalf of the Groupe Francophone de Cytogénétique Hématologique (GFCH) and of the Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO)
Search for more papers by this authorFrancois P. Duhoux
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorGeneviève Ameye
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorCarmen P. Montano-Almendras
de Duve Institute, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorKhadija Bahloula
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorMarie J. Mozziconacci
Institut Paoli-Calmettes, Marseilles, France
Search for more papers by this authorIwona Wlodarska
Centre for Human Genetics, K.U. Leuven, Leuven, Belgium
Search for more papers by this authorLucienne Michaux
Centre for Human Genetics, K.U. Leuven, Leuven, Belgium
Search for more papers by this authorFrank Speleman
Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorChristian Herens
Centre de Génétique humaine, CHU, Liège, Belgium
Search for more papers by this authorKatrina Rack
Institut de Pathologie et de Génétique, Gosselies, Belgium
Search for more papers by this authorSylvie Taviaux
Hôpital Arnaud de Villeneuve, Montpellier, France
Search for more papers by this authorDominique Latinne
Immuno-Haematology Department, Cliniques universitaires Saint- Luc, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorJeanne M. Libouton
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authorJean-Baptiste Demoulin
de Duve Institute, Université catholique de Louvain, Brussels, Belgium
Search for more papers by this authorHélène A. Poirel
Centre for Human Genetics, Cliniques universitaires Saint-Luc, Université catholique de Louvain
Search for more papers by this authoron behalf of the Groupe Francophone de Cytogénétique Hématologique (GFCH) and of the Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO)
Search for more papers by this authorSummary
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.
Supporting Information
Fig S1. Translocation of PRDM16 with IKZF1.
Fig S2. Translocation of PRDM16 with WNT3 or NSF.
Fig S3. Translocation of PRDM16 with THADA.
Fig S4. Translocation of PRDM16 with IGL@.
Table SI. Primers used
Table SII. Complete karyotype and FISH data for the 39 patients with translocations involving PRDM16
Table SIII. Gene expression data
Table SIV. Additional gene expression data
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