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Broad copy neutral-loss of heterozygosity regions and rare recurring copy number abnormalities in normal karyotype-acute myeloid leukemia genomes.
- Source :
-
Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2010 Nov; Vol. 49 (11), pp. 1014-23. - Publication Year :
- 2010
-
Abstract
- 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.<br /> (© 2010 Wiley-Liss, Inc.)
- Subjects :
- Adult
Base Sequence
Chromosomes, Human, Pair 21
Chromosomes, Human, Pair 22
Core Binding Factor Alpha 2 Subunit genetics
DNA Primers
Female
Humans
Karyotyping
Male
Middle Aged
Mutation
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Gene Dosage
Leukemia, Myeloid, Acute genetics
Loss of Heterozygosity
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2264
- Volume :
- 49
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Genes, chromosomes & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 20725993
- Full Text :
- https://doi.org/10.1002/gcc.20810