Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA)

• Published in: Blood Vol. 113; no. 6; pp. 1294 - 1303
• Main Authors: Grubor, Vladimir, Krasnitz, Alex, Troge, Jennifer E., Meth, Jennifer L., Lakshmi, B., Kendall, Jude T., Yamrom, Boris, Alex, Garrick, Pai, Deepa, Navin, Nicholas, Hufnagel, Lisa A., Lee, Yoon-Ha, Cook, Kerry, Allen, Steven L., Rai, Kanti R., Damle, Rajendra N., Calissano, Carlo, Chiorazzi, Nicholas, Wigler, Michael, Esposito, Diane
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.02.2009
• Subjects: ADP-ribosyl Cyclase 1; Chromosome Aberrations; Chromosome Mapping; Chromosomes, Artificial, Bacterial; Chromosomes, Human - genetics; Comparative Genomic Hybridization; DNA, Neoplasm - genetics; Gene Dosage; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genome, Human; Genomic Instability; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Neutrophils - cytology; Neutrophils - metabolism; Oligonucleotide Array Sequence Analysis - methods; Prognosis; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-05-158865

We examined copy number changes in the genomes of B cells from 58 patients with chronic lymphocytic leukemia (CLL) by using representational oligonucleotide microarray analysis (ROMA), a form of comparative genomic hybridization (CGH), at a resolution exceeding previously published studies. We observed at least 1 genomic lesion in each CLL sample and considerable variation in the number of abnormalities from case to case. Virtually all abnormalities previously reported also were observed here, most of which were indeed highly recurrent. We observed the boundaries of known events with greater clarity and identified previously undescribed lesions, some of which were recurrent. We profiled the genomes of CLL cells separated by the surface marker CD38 and found evidence of distinct subclones of CLL within the same patient. We discuss the potential applications of high-resolution CGH analysis in a clinical setting.