Genome-wide DNA methylation profiles distinguish silent from non-silent ACTH adenomas

摘要

Genome-wide DNA methylation profiles split ACTH adenomas into clinically relevant subgroups. Corticotroph adenomas causing either Cushing’s disease (CD) or being clinically silent (SCA) show strong expression of adrenocorticotrophic hormone (ACTH). Scale bar: 100 µm. SCA patients have larger tumors in comparison to CD as measured by MRI (  c Cumulative copy number alterations (CNA) inferred from the DNA methylation data. Healthy pituitary gland samples derived from the publicly accessible Capper set [ ] were used as controls. Heat map using pairwise Pearson correlation coefficients of the 10,000 most variable CpG features across all 36 samples reveals two distinct CD and SCA clusters and a third group with a clinically heterogeneous picture. No AL = no anterior lobe. -Distributed Stochastic Neighbor Embedding ( -SNE) of all methylation probes indicates that SCA and CDs are distinguishable by their epigenetic profiles. -SNE analysis with all 36 ACTH adenomas merged with the CNS tumor reference cohort from Capper et al. (2018).