title: The expression level of small non-coding RNAs derived from the first exon of protein-coding genes is predictive of cancer status.
abstract: Small non-coding RNAs (smRNAs) are known to be significantly enriched near the transcriptional start sites of genes. However, the functional relevance of these smRNAs remains unclear, and they have not been associated with human disease. Within the cancer genome atlas project (TCGA), we have generated small RNA datasets for many tumor types. In prior cancer studies, these RNAs have been regarded as transcriptional "noise," due to their apparent chaotic distribution. In contrast, we demonstrate their striking potential to distinguish efficiently between cancer and normal tissues and classify patients with cancer to subgroups of distinct survival outcomes. This potential to predict cancer status is restricted to a subset of these smRNAs, which is encoded within the first exon of genes, highly enriched within CpG islands and negatively correlated with DNA methylation levels. Thus, our data show that genome-wide changes in the expression levels of small non-coding RNAs within first exons are associated with cancer.
authors.affiliation: BC Cancer Agency Genome Sciences Centre, Vancouver, BC, Canada.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Zovoilis
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mungall
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Richard
authors.initials: R
authors.lastname: Varhol
authors.forename: Andy
authors.initials: A
authors.lastname: Chu
authors.forename: Tina
authors.initials: T
authors.lastname: Wong
authors.forename: Marco
authors.initials: M
authors.lastname: Marra
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D018899:CpG Islands; D019175:DNA Methylation; D005091:Exons; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D024363:Transcription Initiation Site; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D058727:RNA, Small Untranslated