title: aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: coordinate involvement of the regions including BCR and ABL.
abstract: In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene. Another region spanning 22q11-q13 includes the breakpoint cluster region (BCR) of the Philadelphia chromosome. Coordinate 22q11-q13 alterations were observed in 9 of 11 tumors with the 9q34 alteration. Additional regions on 1q and 14q were associated with overall genome-wide copy number changes, while copy number aberrations on chromosome 7p, 7q, and 13q21.1-q31.3 were found associated with this instability only in tumors from patients with a smoking history. Our analysis demonstrates there are a small number of regions of the genome where gain or loss is commonly associated with a tumor's overall level of copy number aberrations. Our finding BCR and ABL located within two of the instability-associated regions, and the involvement of these two regions occurring coordinately, suggests a system akin to the BCR-ABL translocation of CML may be involved in genomic instability in about one-third of human colorectal carcinomas.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Bartos
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gaile
authors.forename: Devin E
authors.initials: DE
authors.lastname: McQuaid
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Conroy
authors.forename: Huferesh
authors.initials: H
authors.lastname: Darbary
authors.forename: Norma J
authors.initials: NJ
authors.lastname: Nowak
authors.forename: Annemarie
authors.initials: A
authors.lastname: Block
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Petrelli
authors.forename: Arnold
authors.initials: A
authors.lastname: Mittelman
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Stoler
authors.forename: Garth R
authors.initials: GR
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D016313:Genes, abl; D042822:Genomic Instability; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics*
chemical_list: C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr