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

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.

Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma

“…The use of cell lines allowed us to study the functional consequences of our analysis, which would not have been possible using only archival specimens. We and others previously reported karyotyping and comparative genome hybridization (CGH) profiles for some PEL (5,(14)(15)(16)(17)(18)(19). Our prior data were array-based and included a survey of known SNVs, which was used as a quality control for this study.…”

Coronin3 regulates gastric cancer invasion and metastasis by interacting with Arp2

“…9 In particular, Coronin3 (Coronin1C) has been associated with metastasis in several cancer types. [10][11][12] In a previous study, we revealed that Coronin3 overexpression promotes GC metastasis both in vitro and in vivo. 13 Metastasis-associated gene analysis indicated that MMP-9 and cathepsin K might play certain roles in the downstream pathways regulated by Coronin3.…”

Benign and Malignant Lymphoproliferative Disorders in HIV/AIDS

“…Gene expression profile studies in primary effusion/body cavity lymphoma have demonstrated a unique profile relative to other aggressive lymphomas; these results tend to substantiate the distinct clinicopathologic distinction of primary effusion/body cavity lymphomas from other lymphomas (Ueda, et al, 2010). Other studies have demonstrated a number of complex cytogenetic abnormalities as well as a reduction in tumour-suppressor gene expression in primary effusion/body cavity lymphoma (Luan, et al, 2010;O'Hara, et al, 2009); these features may further contribute to the aggressiveness of this lesion. Most published cases appear to be treated with CHOP or derivations thereof.…”