title: Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high-resolution array-based comparative genomic hybridization.
abstract: Chronic myelogenous leukemia (CML) evolves from an indolent chronic phase (CP) characterized by the Philadelphia chromosome. Without effective therapy, it progresses to an accelerated phase (AP) and eventually to a fatal blast crisis (BC). To identify the genes involved in stage progression in CML, we performed a genomewide screening of DNA copy number changes in a total of 55 CML patients in different stages with the use of the high-resolution array-based comparative genomic hybridization (array CGH) technique. We constructed Human 1M arrays that contained 3,151 bacterial artificial chromosome (BAC) DNAs, allowing for an average resolution of 1.0 Mb across the entire genome. In addition to common chromosomal abnormalities, array CGH analysis unveiled a number of novel copy number changes. These alterations included losses in 2q26.2-q37.3, 5q23.1-q23.3, 5q31.2-q32, 7p21.3-p11.2, 7q31.1-q31.33, 8pter-p12(p11.2), 9p, and 22q13.1-q13.31 and gains in 3q26.2-q29, 6p22.3, 7p15.2-p14.3, 8p12, 8p21.3, 8p23.2, 8q24.13-q24.21, 9q, 19p13.2-p12, and 22q13.1-q13.32 and occurred at a higher frequency in AP and BC. Minimal copy number changes affecting even a single BAC locus were also identified. Our data suggests that at least a proportion of CML patients carry still-unknown cryptic genomic alterations that could affect a gene or genes of importance in the disease progression of CML. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo,Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hosoya
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanada
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nannya
authors.forename: Kumi
authors.initials: K
authors.lastname: Nakazaki
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Akira
authors.initials: A
authors.lastname: Hangaishi
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000368:Aged; D022202:Chromosomes, Artificial, Bacterial; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D004273:DNA, Neoplasm