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Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes

Authors

  • Vincenza Barresi,

    1. Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università di Catania, Italy
    2. Dipartimento di Scienze Chimiche, Sezione di Biochimica, Università di Catania, Italy
    3. Laboratorio C.I.R.E.S., Facoltà di Medicina, Università di Catania, Italy
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  • Alessandra Romano,

    1. Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università di Catania, Italy
    2. Divisione di Ematologia, Ospedale Ferrarotto, Università di Catania, Italy
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  • Nicolò Musso,

    1. Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università di Catania, Italy
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  • Carmela Capizzi,

    1. Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università di Catania, Italy
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  • Carla Consoli,

    1. Divisione di Ematologia, Ospedale Ferrarotto, Università di Catania, Italy
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  • Maria Paola Martelli,

    1. Istituto di Ematologia, Policlinico Monteluce, Perugia, Italy
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  • Giuseppe Palumbo,

    1. Divisione di Ematologia, Ospedale Ferrarotto, Università di Catania, Italy
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  • Francesco Di Raimondo,

    1. Divisione di Ematologia, Ospedale Ferrarotto, Università di Catania, Italy
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  • Daniele F. Condorelli

    Corresponding author
    1. Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università di Catania, Italy
    2. Dipartimento di Scienze Chimiche, Sezione di Biochimica, Università di Catania, Italy
    3. Laboratorio C.I.R.E.S., Facoltà di Medicina, Università di Catania, Italy
    • Section of Biochemistry and Molecular Biology, Department of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania 95125, Italy
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Abstract

We analyzed, by the latest high-resolution SNP arrays, 19 Normal Karyotype (NK)-AML patients at diagnosis (Dx) and remission (R) phases, to determine the number of tumor-associated copy number abnormalities (CNAs) and copy neutral-loss of heterozygosity (CN-LOH) regions per patient and to identify possible recurring genomic abnormalities. The number of tumor-associated CNAs was determined after comparison of matched Dx/R samples using stringent conditions able to reduce the number of false positive CNAs. With the exception of a single outlier case, a low number of CNAs per patient was detected (median value of 1 somatic loss or gain per patient). However, a high prevalence of CNAs (60–70% of the patients showed at least one tumor-associated gain or loss) and few recurring CNAs were observed, thus providing new hints towards identification of cooperating mutations. An extensive search of all tumor-associated CN-LOH regions >1 Mb revealed only three broad regions (terminal 12Mb of 22q, terminal 27Mb of 1p and the whole chromosome 21) in three patients out of 19 (16%). CN-LOH of the whole chromosome 21 was responsible for homozygosity of a missense mutation (R80C) of RUNX1/AML1. Our study suggests that a relative submicroscopic copy number stability NK-AML genomes is associated with low recurrence of specific CNAs and CN-LOH in NK-AML patient population. Sequencing of candidate genes in the identified CNAs and CN-LOH regions should be considered a priority in the search of novel driver mutations of AML. © 2010 Wiley-Liss, Inc.

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