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Broad copy neutral‐loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype‐acute myeloid leukemia genomes
Author(s) -
Barresi Vincenza,
Romano Alessandra,
Musso Nicolò,
Capizzi Carmela,
Consoli Carla,
Martelli Maria Paola,
Palumbo Giuseppe,
Di Raimondo Francesco,
Condorelli Daniele F.
Publication year - 2010
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20810
Subject(s) - loss of heterozygosity , karyotype , myeloid leukemia , biology , copy number variation , cancer research , genetics , genome , chromosome , gene , allele
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.