Paper - Review

DOI: 10.1038/s41467-021-20907-z

Abstract

❓: The evolution
← of 1⃣ DNA methylome 2⃣ methylation intra-tumor heterogeneity
← during early carcinogenesis of LUAD
→ has not been systematically studied

❗: performed → reduced representative bisulfite sequencing
← of 1⃣ invasive LUAD 2⃣ its precursors

∴ Observed → 1⃣ gradual increase of methylation aberrations 2⃣ significantly higher level of methylation ITH
← in later-stage lesions

❗: the phylogenetic patterns
← inferred from methylation aberrations
→ resemble those ← based on somatic mutations
∴ 1⃣ parallel methylation 2⃣ genetic evolution

❗: Higher ratio ← of 1⃣ T regulatory cells 2⃣ CD8+ T cells ← in later-stage diseases
∵ De-convolution
∴ Progressive immuno-suppression ← with neoplastic progression

❗: Increased global hypo-methylation is associated
← with higher 1⃣ mutation burden 2⃣ copy number variation burden 3⃣ AI burden 4⃣ Treg/CD8 ratio

∴ The potential impact of methylation
← on 1⃣ chromosomal instability 2⃣ mutagenesis 3⃣ tumor immune micro-environment
← during early carcinogenesis of LUAD

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