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Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high‐resolution array‐based comparative genomic hybridization
Author(s) -
Hosoya Noriko,
Sanada Masashi,
Nannya Yasuhito,
Nakazaki Kumi,
Wang Lili,
Hangaishi Akira,
Kurokawa Mineo,
Chiba Shigeru,
Ogawa Seishi
Publication year - 2006
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.20303
Subject(s) - comparative genomic hybridization , biology , chronic myelogenous leukemia , copy number variation , genetics , locus (genetics) , copy number analysis , chromosome , genome , gene , leukemia
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.