An Integrative Analysis of the Age-Associated Genomic, Transcriptomic and Epigenetic Landscape across Cancers

Abstract

Age is the most important risk factor for cancer, as cancer incidence and mortality increase with age. However, how molecular alterations in tumours differ among patients of different age remains largely unexplored. Here, using data from The Cancer Genome Atlas, we comprehensively characterised genomic, transcriptomic and epigenetic alterations in relation to patients age across cancer types. We showed that tumours from older patients present an overall increase in genomic instability, somatic copy-number alterations (SCNAs) and somatic mutations. Age-associated SCNAs and mutations were identified in several cancer-driver genes across different cancer types. The largest age-related genomic differences were found in gliomas and endometrial cancer. We identified age-related global transcriptomic changes and demonstrated that these genes are controlled by age-associated DNA methylation changes. This study provides a comprehensive view of age-associated alterations in cancer and underscores age as an important factor to consider in cancer research and clinical practice.

An integrative analysis of the age-associated multi-omic landscape across cancers

“…The custom scripts for data analysis and generate figures are available at https://github. com/maglab/Age-associated_cancer_genome 80 and released at https://doi.org/10.5281/ zenodo.4564690.…”

Age Influences on the Molecular Presentation of Tumours

“…Combined with similar reports of sex-and ancestry-associated differences in cancer genomes 40,71 , these data reveal a set of host influences on the mutational characteristics of tumours. Indeed, a study in simultaneous preparation by Chatsirisupachai et al describes corroborating evidence of age-associated differences in the genome and transcriptome, as well as age-specific differences in methylation and gene expression control 72 . Together, we find that characteristics of the tumour host appears to influence all aspects of the tumour molecular profile and that some of these lead to age-specific transcriptomic and clinical impacts.…”