Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes
Article first published online: 19 AUG 2010
Copyright © 2010 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 49, Issue 11, pages 1014–1023, November 2010
How to Cite
Barresi, V., Romano, A., Musso, N., Capizzi, C., Consoli, C., Martelli, M. P., Palumbo, G., Di Raimondo, F. and Condorelli, D. F. (2010), Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes. Genes Chromosom. Cancer, 49: 1014–1023. doi: 10.1002/gcc.20810
- Issue published online: 13 SEP 2010
- Article first published online: 19 AUG 2010
- Manuscript Accepted: 29 JUN 2010
- Manuscript Received: 9 MAR 2010
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.