SNP arrays in matched diagnosis/remission samples of normal karyotype-acute myeloid leukemia

We analysed, by last-generation high-resolution SNP arrays, Normal Karyotype (NK)-AML patients at diagnosis (Dx) and remission (R) phases, in order 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 detemined after comparison of 11 matched Dx/R samples using stringent conditions able to reduce the number of false positive CNAs. 8 additional unmatched Dx samples were included in the analysis of recurring CNAs and for detection of broad CN-LOH segments. 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 1 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 CN-LOH regions > 1 Mb revealed only 3 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. Nineteen AML bone marrow samples were collected at the time of diagnosis (>90% blasts), defined as karyotypically-normal on the basis of standard metaphase cytogenetics (MC) and analysed by the Affymetrix SNP 6.0 arrays. In 11 of such cases (matched Dx) we obtained a bone marrow sample at the remission phase (matched R) of comparable high quality as evaluated by Contrast QC and MAPD values. In 8 cases (unmatched Dx) the corresponding R sample was not available or was not of comparable quality. As a reference set the publicly available data from 270 HapMap individuals were used.