Selection of tRNA Genes in Human Breast Tumours Varies Substantially between Individuals

SIMPLE SUMMARY: Elevated expression of many tRNAs is a consistent feature of breast cancer. As each tRNA is encoded by multiple genes, we investigate whether the same genes are always overexpressed in each breast tumour, or whether distinct members of a gene family become activated from one tumour to the next. We find considerable variation between tumours as to which family members undergo activation, whereas familial patterns show much more consistency. A significant correlation is found between patient prognosis and the expression levels of specific tRNAs. ABSTRACT: Abnormally elevated expression of tRNA is a common feature of breast tumours. Rather than a uniform increase in all tRNAs, some are deregulated more strongly than others. Elevation of particular tRNAs has been associated with poor prognosis for patients, and experimental models have demonstrated the ability of some tRNAs to promote proliferation or metastasis. Each tRNA isoacceptor is encoded redundantly by multiple genes, which are commonly dispersed across several chromosomes. An unanswered question is whether the consistently high expression of a tRNA in a cancer type reflects the consistent activation of the same members of a gene family, or whether different family members are activated from one patient to the next. To address this question, we interrogated ChIP-seq data to determine which tRNA genes were active in individual breast tumours. This revealed that distinct sets of tRNA genes become activated in individual cancers, whereas there is much less variation in the expression patterns of families. Several pathways have been described that are likely to contribute to increases in tRNA gene transcription in breast tumours, but none of these can adequately explain the observed variation in the choice of genes between tumours. Current models may therefore lack at least one level of regulation.