title: High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression.
abstract: We have undertaken a genome-wide single nucleotide polymorphism (SNP) array analysis of 41 chronic myeloid leukemia (CML) patients. In total, 44 regions of uniparental disomy (UPD) >3 Mb were identified in 24 of 32 patients in chronic phase (CP), and 21 regions of UPD >3 Mb were identified in 13 of 21 patients in blast crisis (BC). Chromosome 8 had the highest frequency of UPD regions in both CP and BC samples. Eight recurrent regions of UPD were observed among the 41 patients, with chromosome 8 showing the highest frequency. Ten regions of copy number change (CNC) >3 Mb were observed in 4 of 21 patients in BC, whereas none were observed in CP. We have identified several recurrent regions of UPD and CNC in CML that may be of pathogenetic importance. Overrepresentation of genomic aberrations (UPD and copy number gain) mapping to chromosome 8 was observed. Selected candidate genes mapping within the aberrant genomic regions were sequenced and mutation of the TP53 gene was observed in one case in BC and of the ASXL1 gene in 6 of 41 cases in CP or BC. Mutation of ASXL1 represents an important new molecular abnormality in CML.
authors.affiliation: LRF Molecular Haematology Unit, NDCLS, University of Oxford, John Radcliffe Hospital, Oxford, UK. jacqueline.boultwood@ndcls.ox.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Boultwood
authors.forename: J
authors.initials: J
authors.lastname: Perry
authors.forename: R
authors.initials: R
authors.lastname: Zaman
authors.forename: C
authors.initials: C
authors.lastname: Fernandez-Santamaria
authors.forename: T
authors.initials: T
authors.lastname: Littlewood
authors.forename: R
authors.initials: R
authors.lastname: Kusec
authors.forename: A
authors.initials: A
authors.lastname: Pellagatti
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
authors.forename: J S
authors.initials: JS
authors.lastname: Wainscoat
mesh_terms: D001752:Blast Crisis / Q000235:genetics*; D018450:Disease Progression; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: C473949:ASXL1 protein, human; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53