title: Whole-genome scanning by array comparative genomic hybridization as a clinical tool for risk assessment in chronic lymphocytic leukemia.
abstract: Array-based comparative genomic hybridization (array CGH) provides a powerful method for simultaneous genome-wide scanning and prognostic marker assessment in chronic lymphocytic leukemia (CLL). In the current study, commercially available bacterial artificial chromosome and oligonucleotide array CGH platforms were used to identify chromosomal alterations of prognostic significance in 174 CLL cases. Tumor genomes were initially analyzed by bacterial artificial chromosome array CGH followed by confirmation and breakpoint mapping using oligonucleotide arrays. Genomic changes involving loci currently interrogated by fluorescence in situ hybridization (FISH) panels were detected in 155 cases (89%) at expected frequencies: 13q14 loss (47%), trisomy 12 (13%), 11q loss (11%), 6q loss (7.5%), and 17p loss (4.6%). Genomic instability was the second most commonly identified alteration of prognostic significance with three or more alterations involving loci not interrogated by FISH panels identified in 37 CLL cases (21%). A subset of 48 CLL cases analyzed by six-probe FISH panels (288 total hybridizations) was concordant with array CGH results for 275 hybridizations (95.5%); 13 hybridizations (4.5%) were discordant because of clonal populations that comprised less than 30% of the sample. Array CGH is a powerful, cost-effective tool for genome-wide risk assessment in the clinical evaluation of CLL.
authors.affiliation: The University of Texas Health Science Center at San Antonio, Department of Pathology, Mail Code 7750, 7703 Floyd Curl Dr., San Antonio, TX, USA. gunn@uthscsa.edu
authors.forename: Shelly R
authors.initials: SR
authors.lastname: Gunn
authors.forename: Mansoor S
authors.initials: MS
authors.lastname: Mohammed
authors.forename: Mercedes E
authors.initials: ME
authors.lastname: Gorre
authors.forename: Philip D
authors.initials: PD
authors.lastname: Cotter
authors.forename: Jaeweon
authors.initials: J
authors.lastname: Kim
authors.forename: David W
authors.initials: DW
authors.lastname: Bahler
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Preobrazhensky
authors.forename: Russell A
authors.initials: RA
authors.lastname: Higgins
authors.forename: Aswani R
authors.initials: AR
authors.lastname: Bolla
authors.forename: Sahar H
authors.initials: SH
authors.lastname: Ismail
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: Eric
authors.initials: E
authors.lastname: Eldering
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: Clemens H M
authors.initials: CH
authors.lastname: Mellink
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Schlette
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Robetorye
mesh_terms: D000465:Algorithms; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics*; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment