Purpose:To determine the recurring DNA copy number alterations (CNAs) in classical Hodgkin lymphoma (HL) by microarray-based comparative genomic hybridization (aCGH) using laser capture micro-dissected CD30+ Hodgkin/Reed-Sternberg (HRS) cells. Experimental Design:Archived tissues from 27 CD30+ HL plus control samples were analyzed by DNA microarrays. The HL molecular karyotypes were compared to the genomic profiles of germinal center B cells and treatment outcome (chemotherapy responsive vs. primary refractory disease). Results:Gains and losses observed in >35% of HL samples were localized respectively to 22 and 12 chromosomal regions. Frequent gains (>65%) were associated with growth and proliferation, NF-κB activation, cell cycle control, apoptosis, and immune and lymphoid development. Frequent losses (>40%) observed encompassed tumor suppressor genes (SPRY1, NELL1, ID4), transcriptional repressors (TXNIP), SKP2 (ubiquitin ligase component) and an antagonist of NF-κB activation (PPARGC1A). In comparison to the germinal center profiles, the most frequent imbalances in HL were losses in 5p13 (AMACR, GDNF, SKP2), and gains in 7q36 (SHH) and 9q34 (ABL1, CDK9, LCN2, PTGES). Gains (>35%) in the HL chemoresponsive patients housed genes known to regulate T-cell trafficking or NF-κB activation (CCL22, CX3CL1, CCL17, DOK4 and IL10), whereas the refractory samples showed frequent loss of 4q27 (IL2/IL21), 17p12 and 19q13.3 gain (BCL3/RELB). Conclusions:We identified non-random CNAs in the molecular karyotypes of classical HL. Several recurring genetic lesions correlated with disease outcome. These findings may be useful prognostic markers in the counseling and management of patients and for the development of novel therapeutic approaches in primary refractory HL.
- Received April 23, 2010.
- Revision received August 23, 2010.
- Accepted September 3, 2010.
- Copyright © 2011, American Association for Cancer Research.