EBV and 1q Gains Affect Gene and miRNA Expression in Burkitt Lymphoma

• Published in: Viruses Vol. 15; no. 9; p. 1808
• Main Authors: Akyüz, Nuray, Janjetovic, Snjezana, Ghandili, Susanne, Bokemeyer, Carsten, Dierlamm, Judith
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 25.08.2023; MDPI
• Subjects: 1q gains; Breakpoints; Burkitt lymphoma; Burkitt's lymphoma; Cancer; Chromosome 1; Chromosome aberrations; Chromosomes; Cloning; EBV; Epstein-Barr virus; FISH; Gene expression; Genetic aspects; Health aspects; Hybridization; Immunoglobulins; Lymphoma; Mcl-1 protein; Medical prognosis; Medical research; Medicine, Experimental; MicroRNA; MicroRNAs; miRNA; Patients; Physiological aspects; qPCR; Up-regulation; Germany; Africa
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15091808

Abnormalities of the long arm of chromosome 1 (1q) represent the most frequent secondary chromosomal aberrations in Burkitt lymphoma (BL) and are observed almost exclusively in EBV-negative BL cell lines (BL-CLs). To verify chromosomal abnormalities, we cytogenetically investigated EBV-negative BL patient material, and to elucidate the 1q gain impact on gene expression, we performed qPCR with six 1q-resident genes and analyzed miRNA expression in BL-CLs. We observed 1q aberrations in the form of duplications, inverted duplications, isodicentric chromosome idic(1)(q10), and the accumulation of 1q12 breakpoints, and we assigned 1q21.2–q32 as a commonly gained region in EBV-negative BL patients. We detected MCL1, ARNT, MLLT11, PDBXIP1, and FCRL5, and 64 miRNAs, showing EBV- and 1q-gain-dependent dysregulation in BL-CLs. We observed MCL1, MLLT11, PDBXIP1, and 1q-resident miRNAs, hsa-miR-9, hsa-miR-9*, hsa-miR-92b, hsa-miR-181a, and hsa-miR-181b, showing copy-number-dependent upregulation in BL-CLs with 1q gains. MLLT11, hsa-miR-181a, hsa-miR-181b, and hsa-miR-183 showed exclusive 1q-gains-dependent and FCRL5, hsa-miR-21, hsa-miR-155, hsa-miR-155*, hsa-miR-221, and hsa-miR-222 showed exclusive EBV-dependent upregulation. We confirmed previous data, e.g., regarding the EBV dependence of hsa-miR-17-92 cluster members, and obtained detailed information considering 1q gains in EBV-negative and EBV-positive BL-CLs. Altogether, our data provide evidence for a non-random involvement of 1q gains in BL and contribute to enlightening and understanding the EBV-negative and EBV-positive BL pathogenesis.