DNA Methylation loss coupled with mitotic cell division promotes immune evasion of tumours with high mutation load

Study ID Alternative Stable ID Type
EGAS00001003731 Other

Study Description

Mitotic cell division increases tumour mutation burden and copy number load with a positive and inverse correlation, respectively, with the clinical benefit of immunotherapy. Markers of cell division correlate also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA ... (Show More)

Study Datasets 2 datasets.

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Dataset ID Description Technology Samples
This data includes whole exome sequencing of matched normal-tumor samples of patients who have received immunotherapy. '-1' refers to matched normal sample and '-2' refers to matched tumor sample.
Illumina HiSeq 2500 294
This data incldues matched exome data of patients who received immunotherapy.
Illumina HiSeq 2500 120

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