Regional Oncology Research Center

Johns Hopkins University, Baltimore MD

Investigators

Linked publications, trials & patents

Abstract

Non-Hodgkin Lymphoma (NHL) occurs more frequently in people living with HIV (PLWH) than in the general population. Yet, the diagnosis of lymphoma is more challenging, and often delayed, in this high-risk group. The aggressive nature of HIV(+) NHL means that prolonged diagnostic intervals can result in irreversible clinical decline that limits curative-intent treatment options. Detection of cell-free circulating tumor DNA found in plasma may serve as a diagnostic biomarker that could expedite definitive lymphoma diagnoses. This proposal aims to use existing biospecimens to discover novel diagnostic biomarkers for HIV(+) EBV(+) NHL. While sophisticat-ed sequencing methods are proposed, the long-term objective is to develop a simple and inexpensive assay that could be implemented domestically and internationally to accelerate the diagnosis of HIV-associated lym-phoma. EBV-associated NHL accounts for ~50% of NHL in PLWH. Plasma EBV DNA is often found in circulation at the time of presentation. However, a substantial fraction of PLWH without EBV(+) disease will also have high levels of circulating EBV DNA, which indicates more specific tumor markers are needed. In non-HIV settings, it is clear that CpG methylated EBV DNA differentiates the presence of virion versus tumor DNA, and may dis-tinguish among tumor types. However, comprehensive assessment of EBV DNA methylation has not been un-dertaken in PLWH. We anticipate that fine mapping the EBV methylome in PLWH will reveal differentially methylated regions of the viral genome that can distinguish PLWH with EBV(+) NHL from PLWH without lym-phoma, but with high-copy plasma EBV DNA, and may also identify uniquely methylated regions that can dis-tinguish NHL subtypes. Two aims are proposed: aim 1 will investigate the tumor EBV methylome in HIV(+) NHL specimens by whole genome bisulfite sequencing to determine shared and unique regions of hyper- or hypo-methylation that may distinguish lymphoma subtypes; aim 2 will investigate the plasma EBV methylome in PLWH with and without EBV(+) NHL to identify consistent regions of hyper- or hypomethylation that may dis-tinguish PLWH with lymphoma from those without. Findings from this study are likely to identify novel diagnostic biomarkers for HIV(+) NHL, and will improve our understanding of the development of HIV-associated EBV(+) lymphoma.