Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/155229
Title: DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load
Author: Jung, Hyunchul
Kim, Hong Sook
Kim, Jeong Yeon
Sun, Jong-Mu
Ahn, Jin Seok
Ahn, Myung-Ju
Park, Keunchil
Esteller, Manel
Lee, Se-Hoon
Choi, Jung Kyoon
Keywords: ADN
Metilació
Genètica
Immunologia
Tumors
DNA
Methylation
Genetics
Immunology
Tumors
Issue Date: 19-Sep-2019
Publisher: Nature Publishing Group
Abstract: Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates 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 methylation alterations implicate epigenetic modulation in precision immunotherapy.
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-12159-9
It is part of: Nature Communications, 2019, vol. 10, num. 1, p. 4278
URI: http://hdl.handle.net/2445/155229
Related resource: https://doi.org/10.1038/s41467-019-12159-9
ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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