Age Influences on the Molecular Presentation of Tumours

Abstract

<jats:title>Abstract</jats:title><jats:p>Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterize them we analyzed age-biases in the somatic mutational landscape of 12,774 tumours across 33 tumour-types. Age influences both the number of mutations in a tumour and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes. A subset of known cancer driver genes were mutated in age-biased patterns, and these alter the transcriptome and predict for clinical outcomes. These effects were most striking in lower grade glioma where <jats:italic>ATRX</jats:italic> mutation is a strongly age-dependent prognostic biomarker. Though cancer genome sequencing data is not well-balanced in epidemiologic factors, these data suggest that age shapes the somatic mutational landscape of cancer, with clear clinical implications.</jats:p>

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

“…During the preparation of our manuscript, a study based on a similar concept has been released by Li et al 60 . In this work, Li et al used TCGA and the recent pan-cancer analysis of whole genomes data to study age-associated genomic differences in cancer.…”

Biomarkers In Brain Tumors With Focus On Glioblastoma

“…A recent study showed that the most common type of mutation in GBM is a C>T substitution, closely related to aging, and that mutational profiles of gliomas largely depend on the patient's age, e.g. there is association between EGFR-gains and loss of CDKN2A in GBM and mutations in ATRX in LGG (4). The inability of cells to repair damaged DNA is believed to be a major cause of aging (112), which further supports the strong position of age as a prognostic factor.…”

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Pan-cancer transcriptomic analysis reveals a tissue-specific loss of identity

“…Previous studies demonstrated that there are important molecular differences when considering the age of cancer patients (15,(31)(32)(33). Then, considering that perhaps the loss of tissue identity occurs in ageing, we tested the hypothesis that the patient's age influences the pattern of expression of specificity genes.…”