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Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas

Hu, Xin; Estecio, Marcos R; Chen, Runzhe; Reuben, Alexandre; Wang, Linghua; Fujimoto, Junya; Carrot-Zhang, Jian; ... Zhang, Jianjun; + view all (2021) Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas. Nature Communications , 12 , Article 687. 10.1038/s41467-021-20907-z. Green open access

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Abstract

The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8 + T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas.

Type: Article
Title: Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-021-20907-z
Publisher version: https://doi.org/10.1038/s41467-021-20907-z
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, INTRATUMOR HETEROGENEITY, EPIGENETIC REGULATION, METHYLATION, CANCER, HYPOMETHYLATION, PROGRESSION, ANNOTATION, LANDSCAPE, TUMORS, CELLS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10160827
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