Abstract
Primary central nervous system lymphomas (PCNSL) have a dramatically increased prevalence among persons living with AIDS and are known to be associated with human Epstein Barr virus (EBV) infection. Previous work suggests that in some cases, co-infection with other viruses may be important for PCNSL pathogenesis. Viral transcription in tumor samples can be measured using next generation transcriptome sequencing. We demonstrate the ability of transcriptome sequencing to identify viruses, characterize viral expression, and identify viral variants by sequencing four archived AIDS-related PCNSL tissue samples and analyzing raw sequencing reads. EBV was detected in all four PCNSL samples and cytomegalovirus (CMV), JC polyomavirus (JCV), and HIV were also discovered, consistent with clinical diagnoses. CMV was found to express three long non-coding RNAs recently reported as expressed during active infection. Single nucleotide variants were observed in each of the viruses observed and three indels were found in CMV. No viruses were found in several control tumor types including 32 diffuse large B-cell lymphoma samples. This study demonstrates the ability of next generation transcriptome sequencing to accurately identify viruses, including DNA viruses, in solid human cancer tissue samples.
Highlights
Non-Hodkin’s lymphomas are tied with Kaposi sarcoma as the most common AIDS-defining cancers
No viruses were found in chronic lymphocytic leukemia (CLL) or non-small cell lung carcinoma (NSCLC) negative controls, but HIV 1 and synthetic construct were found as expected in one transduced cord blood sample which served as a positive control [SRA:SRP017364]
No viruses were identified in a set of 32 diffuse large B-cell lymphoma (DLBCL) samples downloaded from the Cancer Genome Characterization Initiative (Table S1)
Summary
Non-Hodkin’s lymphomas are tied with Kaposi sarcoma as the most common AIDS-defining cancers. Primary central nervous system lymphomas (PCNSL) accounted for 7% of all AIDS cancers in the early HAART era and have a roughly 1000-fold increased prevalence in persons living with AIDS [1,2]. While the incidence rate of PCNSL has fallen by nearly 90% since the advent of HAART, immunocompromised individuals continue to be at risk for this aggressive cancer [3]. EBV efficiently immortalizes Bcells in vitro and is associated with cancers besides PCNSL such as Burkitt’s and Hodgkin lymphomas, nasopharyngeal carcinoma, and others [8,9,10]. It has been hypothesized that viruses in addition to EBV may play a role in PCNSL [11,12]
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