Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes.
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.
Barresi
Vincenza
V
Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università di Catania, Italy.
Romano
Alessandra
A
Musso
Nicolò
N
Capizzi
Carmela
C
Consoli
Carla
C
Martelli
Maria Paola
MP
Palumbo
Giuseppe
G
Di Raimondo
Francesco
F
Condorelli
Daniele F
DF
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
D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; C493728:RUNX1 protein, human