期刊
JOURNAL OF PATHOLOGY
卷 222, 期 2, 页码 166-179出版社
WILEY
DOI: 10.1002/path.2752
关键词
primary effusion lymphoma; CGH; SELPLG; CORO1C; gene amplification
资金
- Leukaemia & Lymphoma Research, UK
- Kay Kendall Leukaemia Research Fund, UK
- Leukaemia & Lymphoma Society USA
- National Institute for Health Research Cambridge Biomedical Research Center
- French Association pour la Recherche sur le Cancer (ARC)
- Health Foundation
- Royal College of Pathologists
- Pathological Society of Great Britain and Ireland
- Cambridge Fund for the Prevention of Disease (CAMPOD)
- Openwork Foundation, Swindon
Primary effusion lymphoma (PEL) is associated with Kaposi sarcoma herpesvirus (KSHV) but its pathogenesis is poorly understood. Many KSHV-associated products can deregulate cellular pathways commonly targeted in cancer. However, KSHV infection alone is insufficient for malignant transformation. PEL also lacks the chromosomal translocations seen in other lymphoma subtypes. We investigated 28 PELs and ten PEL cell lines by 1 Mb resolution array comparative genomic hybridization (CGH) and found frequent gains of 1q21-41 (47%), 4q28.3-35 (29%), 7q (58%), 8q (63%), 11 (32%), 12 (61%), 17q (29%), 19p (34%), and 20q (34%), and losses of 4q (32%), 11q25 (29%), and 14q32 (63%). Recurrent focal amplification was seen at several regions on chromosomes 7, 8, and 12. High-resolution chromosome-specific tile-path array CGH confirmed these findings, and identified selectin-P ligand (SELPLG) and coronin-1C (CORO1C) as the targets of a cryptic amplification at 12q24.11. Interphase FISH and quantitative PCR showed SELPLG/CORO1C amplification (>4 extra copies) and low levels of copy number gain (1-4 extra copies) in 23% of PELs, respectively. Immunohistochemistry revealed strong expression of both SELPLG and coronin-1C in the majority of PELs, irrespective of their gene dosage. SELPLG is critical for cell migration and chemotaxis, while CORO1C regulates actin-dependent processes, thus important for cell motility. Their overexpression in PEL is expected to play an important role in its pathogenesis. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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