Whole-genome scanning by array comparative genomic hybridization as a clinical tool for risk assessment in chronic lymphocytic leukemia

Shelly R. Gunn, Mansoor S. Mohammed, Mercedes E. Gorre, Philip D. Cotter, Jaeweon Kim, David W. Bahler, Sergey N. Preobrazhensky, Russell A. Higgins, Aswani R. Bolla, Sahar H. Ismail, Daphne De Jong, Eric Eldering, Marinus H.J. Van Oers, Clemens H.M. Mellink, Michael J. Keating, Ellen J. Schlette, Lynne V. Abruzzo, Ryan S. Robetorye

Research output: Contribution to journalArticle

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)442-451
Number of pages10
JournalJournal of Molecular Diagnostics
Volume10
Issue number5
DOIs
StatePublished - Sep 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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    Gunn, S. R., Mohammed, M. S., Gorre, M. E., Cotter, P. D., Kim, J., Bahler, D. W., Preobrazhensky, S. N., Higgins, R. A., Bolla, A. R., Ismail, S. H., De Jong, D., Eldering, E., Van Oers, M. H. J., Mellink, C. H. M., Keating, M. J., Schlette, E. J., Abruzzo, L. V., & Robetorye, R. S. (2008). Whole-genome scanning by array comparative genomic hybridization as a clinical tool for risk assessment in chronic lymphocytic leukemia. Journal of Molecular Diagnostics, 10(5), 442-451. https://doi.org/10.2353/jmoldx.2008.080033