title: Whole transcriptome sequencing enables discovery and analysis of viruses in archived primary central nervous system lymphomas.
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.
authors.affiliation: Moores Cancer Center, University of California San Diego, La Jolla, California, United States of America ; Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: DeBoever
authors.forename: Erin G
authors.initials: EG
authors.lastname: Reid
authors.forename: Erin N
authors.initials: EN
authors.lastname: Smith
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.forename: Wilmar
authors.initials: W
authors.lastname: Dumaop
authors.forename: Olivier
authors.initials: O
authors.lastname: Harismendy
authors.forename: Dennis
authors.initials: D
authors.lastname: Carson
authors.forename: Douglas
authors.initials: D
authors.lastname: Richman
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Frazer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000368:Aged; D016543:Central Nervous System Neoplasms / Q000150:complications / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008223:Lymphoma / Q000150:complications / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014780:Viruses / Q000235:genetics* / Q000302:isolation & purification*
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