Locus specific human endogenous retroviruses reveal new lymphoma subtypes.
Bhavya SinghNicholas DopkinsTongyi FeiJez L MarstonStephanie MichaelHelena Reyes-GoparGislaine CurtyJonas J HeymannAmy ChadburnPeter MartinFabio Eudes LealEthel CesarmanDouglas F NixonMatthew L BendallPublished in: bioRxiv : the preprint server for biology (2023)
The heterogeneity of cancers are driven by diverse mechanisms underlying oncogenesis such as differential 'cell-of-origin' (COO) progenitors, mutagenesis, and viral infections. Classification of B-cell lymphomas have been defined by considering these characteristics. However, the expression and contribution of transposable elements (TEs) to B cell lymphoma oncogenesis or classification have been overlooked. We hypothesized that incorporating TE signatures would increase the resolution of B-cell identity during healthy and malignant conditions. Here, we present the first comprehensive, locus-specific characterization of TE expression in benign germinal center (GC) B-cells, diffuse large B-cell lymphoma (DLBCL), Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt lymphoma (BL), and follicular lymphoma (FL). Our findings demonstrate unique human endogenous retrovirus (HERV) signatures in the GC and lymphoma subtypes whose activity can be used in combination with gene expression to define B-cell lineage in lymphoid malignancies, highlighting the potential of retrotranscriptomic analyses as a tool in lymphoma classification, diagnosis, and the identification of novel treatment groups.
Keyphrases
- diffuse large b cell lymphoma
- epstein barr virus
- gene expression
- single cell
- machine learning
- endothelial cells
- poor prognosis
- deep learning
- stem cells
- dna methylation
- induced pluripotent stem cells
- crispr cas
- genome wide
- cell therapy
- mass spectrometry
- human health
- climate change
- combination therapy
- high resolution
- risk assessment
- gas chromatography