SNP-array lesions in core binding factor acute myeloid leukemia

Nicolas Duployez 1, 2, * Elise Boudry-Labis 2, 3 Christophe Roumier 1, 2 Nicolas Boissel 4 Arnaud Petit 5, 6, 7, 8 Sandrine Geffroy 1, 2 Nathalie Helevaut 1, 2 Karine Celli-Lebras 4 Christine Terré 9 Odile Fenneteau 10 Wendy Cuccuini 11 Isabelle Luquet 12 Hélène Lapillonne 5, 6, 7, 13 Catherine Lacombe 14 Pascale Cornillet 15 Norbert Ifrah 16 Hervé Dombret 4 Guy Leverger 5, 6, 7, 8 Eric Jourdan 17 Claude Preudhomme 1, 2, *
Abstract : Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia.
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Nicolas Duployez, Elise Boudry-Labis, Christophe Roumier, Nicolas Boissel, Arnaud Petit, et al.. SNP-array lesions in core binding factor acute myeloid leukemia. Oncotarget, Impact journals, 2018, 9, pp.6478 - 6489. ⟨inserm-01813829⟩

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