An Interferon Response Gene Expression Signature Is Activated in a Subset of Medulloblastomas

Abstract

Recent evidence suggests that cytomegalovirus infection contributes to the development of medulloblastomas. Differential activation of antiviral expression programs in medulloblastomas has not been investigated yet. In this study, we assess the relevance of an antiviral transcriptional response in medulloblastomas. We analyzed a gene expression signature of type I interferon response in three public gene expression data sets of medulloblastomas. Interferon response genes were found to be significantly coordinately regulated in two independent studies. We distilled a signature of 10 interferon response genes from two data sets. This signature exhibited strongly significant gene-versus-gene correlation of expression levels across samples in a third external medulloblastoma data set. Our medulloblastoma IFN signature identified a previously unrecognized patient subgroup partially overlapping the WNT and SHH subtypes proposed by others. We conclude that significant traces of differential activation of antiviral transcriptional response can be found in three independent medulloblastoma patient cohorts. This IFN activation signal often coincides with reduced proliferation scores. Our proposed 10-gene type I IFN response gene signature could help to assess antiviral states in further gene expression data sets of medulloblastomas or other cancers.