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Fig. 3 | Genome Biology

Fig. 3

From: The senescent methylome and its relationship with cancer, ageing and germline genetic variation in humans

Fig. 3

The methylomic signature of cellular senescence shows no association with expression but is shared among methylation signatures of human cancers and ageing. a The number of genes that are both significantly altered in both expression and methylation for senDMPs (coloured vertical line; blue – experiment 1 only, green – experiment 2 only, and purple – agree) against the background model. There is a significant enrichment of genes altered in both gene expression and methylation for those sites that agree while no significant enrichment for those sites which vary in experiment 1 or 2 only. b Scatter plot of the average methylation in normal breast tissue from TCGA for CpGs that are hypermethylated during senescence against those that are hypomethylated in senescence. The three different sites are plotted in three different panels going from left to right: blue – experiment 1 only, green – experiment 2 only, and purple – agree. A negative correlation implies that our senDMP signature is present in these breast samples. c The senescence score was calculated for each of the 73 normal breast tissues and plotted against the log of the expression for CDKN2A (left) and CDKN2B (right). The three different sites are plotted from top to bottom: blue – experiment 1 only, green – experiment 2 only, and purple – agree. d The senescence score was derived from senDMPs and calculated for both normal and tumour breast tissue from TCGA (n = 73). Tumour samples show a much higher senescence score compared to normal samples for the three different set of sites (blue – experiment 1 only, green – experiment 2 only, and purple – agree). e A boxplot of the senescence score for the samples from 11 different cancers (coloured boxes) calculated from the TCGA datasets and the corresponding control tissue for each cancer (white boxes). Each cancer sample shows an increased senescence score compared to the control samples. The three different sites are plotted from top to bottom: blue – experiment 1 only, green – experiment 2 only, and purple – agree. The 11 different cancers are Thyroid vThyroid Carcinoma (THCA), Kidney v Kidney renal clear cell Carcinoma (KIRC), Endometrial v Uterine Corpus Endrometrioid Carcinoma (UCEC), Lung v Lung Adenocarcinoma (LUAD), Head/Neck v Head/Neck Squamous Cell Carcinoma (HNSC), Lung v Lung Squamous Cell Carcinoma (LUSC), Colon v Colon Adenocarcinoma (COAD), Kidney v Kidney Renal Papillary Cell Carcinoma (KIRP) or Kidney Chromophobe (KICH), Prostate v Prostate Adenocarcinoma (PRAD), Liver v Liver Hepatocellular Carcinoma (LIHC). f Scatter plot of the senescence score for normal breast tissue against the age of the sample. A significant correlation between the senescence score and age is observed for all sets of sites, with older samples producing a higher senescence score. The three different sites are plotted from left to right: blue – experiment 1 only, green – experiment 2 only, and purple – agree

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