title: Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes.
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.
authors: Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università di Catania, Italy.
authors: Vincenza
authors: V
authors: Barresi
authors: Alessandra
authors: A
authors: Romano
authors: Nicolò
authors: N
authors: Musso
authors: Carmela
authors: C
authors: Capizzi
authors: Carla
authors: C
authors: Consoli
authors: Maria Paola
authors: MP
authors: Martelli
authors: Giuseppe
authors: G
authors: Palumbo
authors: Francesco
authors: F
authors: Di Raimondo
authors: Daniele F
authors: DF
authors: Condorelli
mesh_terms: D000328:Adult; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21; D002892:Chromosomes, Human, Pair 22; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D017931:DNA Primers; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; C493728:RUNX1 protein, human