Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration.

TitlePrimary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration.
Publication TypeJournal Article
Year of Publication2010
AuthorsLuan S-L, Boulanger E, Ye H, Chanudet E, Johnson N, Hamoudi RA, Bacon CM, Liu H, Huang Y, Said J, Chu P, Clemen CS, Cesarman E, Chadburn A, Isaacson PG, Du M-Q
JournalJ Pathol
Volume222
Issue2
Pagination166-79
Date Published2010 Oct
ISSN1096-9896
KeywordsCell Movement, Chromosome Aberrations, Cocarcinogenesis, Comparative Genomic Hybridization, Epstein-Barr Virus Infections, Gene Amplification, Gene Expression Profiling, Humans, Lymphoma, Primary Effusion, Membrane Glycoproteins, Microfilament Proteins, Neoplasm Proteins, Tumor Cells, Cultured
Abstract

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.

DOI10.1002/path.2752
Alternate JournalJ Pathol
PubMed ID20690162
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Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.

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