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

Genes Chromosomes Cancer. 2010 Nov;49(11):1014-23.Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes.Barresi V, Romano A, Musso N, Capizzi C, Consoli C, Martelli MP, Palumbo G, DiRaimondo F, Condorelli DF.Laboratorio sui Sistemi Complessi, Scuola Superiore di Catania, Università diCatania, Italy.We analyzed, by the latest high-resolution SNP arrays, 19 Normal Karyotype(NK)-AML patients at diagnosis (Dx) and remission (R) phases, to determine thenumber of tumor-associated copy number abnormalities (CNAs) and copy neutral-lossof heterozygosity (CN-LOH) regions per patient and to identify possible recurringgenomic abnormalities. The number of tumor-associated CNAs was determined aftercomparison 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 lownumber of CNAs per patient was detected (median value of 1 somatic loss or gainper patient). However, a high prevalence of CNAs (60-70% of the patients showedat least one tumor-associated gain or loss) and few recurring CNAs were observed,thus providing new hints towards identification of cooperating mutations. Anextensive search of all tumor-associated CN-LOH regions >1 Mb revealed only threebroad regions (terminal 12Mb of 22q, terminal 27Mb of 1p and the whole chromosome21) in three patients out of 19 (16%). CN-LOH of the whole chromosome 21 wasresponsible for homozygosity of a missense mutation (R80C) of RUNX1/AML1. Ourstudy suggests that a relative submicroscopic copy number stability NK-AMLgenomes is associated with low recurrence of specific CNAs and CN-LOH in NK-AMLpatient population. Sequencing of candidate genes in the identified CNAs andCN-LOH regions should be considered a priority in the search of novel drivermutations of AML.© 2010 Wiley-Liss, Inc.PMID: 20725993 [PubMed - indexed for MEDLINE]