Tumor type (number of methylation groups) | Methylation subgroup | Genomic aberrations | Methylation pattern* | Comments | References |
---|---|---|---|---|---|
AML | High | IDH1/2 or TET2 mutations | A | Associated with patients presenting with an intermediate-risk karyotype | |
 |  |  |  | Co-occurrence of IDH1/2 and NPM1 mutations is associated with good clinical outcome |  |
Bladder urothelial (3) | High | RB1 mutations |  | Smoking-pack years as predictor of CIMP phenotype Frequent mutations in chromatin regulators such as MLL2, ARID1A, KDM6A, and EP300†Mutations in chromatin regulators were more frequent than in any other TCGA tumor | [35] |
Low | ↑ TP53 mutations | B | |||
Breast (5) | B-CIMP | ↓ mutation rate |  | Luminal ER/PR-positive tumors | |
Low metastatic risk and better clinical outcome | |||||
Enriched for genes targeted by the PRC2 (e.g. SUZ12 and EZH2) | |||||
B-CIMP-negative | ↑ TP53 mutations | B | Basal-like tumors (ER/PR-negative) | ||
High metastatic risk and poor clinical outcome | |||||
Cholangiocarcinoma | High | IDH1 and/or IDH2 mutations | A | Longer survival | [47] |
Chondrosarcoma | High | IDH1 and/or IDH2 mutations | A | Â | |
Colorectal (4) | CIMP-H | MLH1 hypermethylation | C | MSI | |
Right/ascending colonic region | |||||
↑ mutation rate | |||||
↑ BRAFV600E mutation | |||||
Good prognosis | |||||
↑ BRAFV600E mutation | |||||
CIMP-L | KRAS mutations | Â | CIN (non-MSI) | ||
Poor prognosis | |||||
Two non-CIMP | ↑ TP53 mutations | B | Anatomic origins distinct from CIMP groups | ||
↑ SCNAs | |||||
Endometrial (4) | High | MLH1 hypermethylation | C | MSI | [33] |
ARID5B mutations | |||||
↑ mutation rate | |||||
Low | ↑ TP53 mutations | B | Serous-like tumors | ||
↑ SCNAs |  | Poor prognosis | |||
Two non-methylated | ↑ POLE mutations |  | Endometrioid tumors |  | |
↑ SCNAs | ARID1A and PTEN mutations were present in all groups without high TP53 mutations | ||||
Gastric (4) | EBV-CIMP | ↑ PIK3CA, ARID1A and BCOR mutations |  | EBV-positive tumors Highest frequency of hypermethylation events among TCGA tumors | [30] |
CDKN2A hypermethylation | |||||
Amplifications of JAK2, CD274 and PDCD1LG2 | |||||
Gastric CIMP | MLH1 silencing | C | MSI | ||
↑ mutation rate | |||||
Cluster 3-low | RHOA and CDH1 mutations | Â | Enriched for the diffuse histological variant | ||
Genomically stable | Also fusions involving RHO-family GTPase-activating proteins | ||||
Cluster 4-low | ↑ TP53 mutation | B | CIN | ||
Focal amplifications of receptor tyrosine kinases | |||||
Glioblastoma (6) | G-CIMP | IDH1 mutations | A | Secondary tumors with proneural expression | |
ATRX mutations | |||||
MYC mutations and amplifications | |||||
Younger age at diagnosis | |||||
Better survival rates | |||||
G-CIMP negative proneural | No IDH1 mutations | Â | Relative hypomethylation | ||
PDGFRA amplifications | Proneural subtype cases without IDH1 mutations | ||||
Pediatric glioblastoma (6) | Global loss of methylation at non-promoter regions | H3F3A mutations | Â | H3F3A mutations are mutually exclusive with IDH1 mutations and are associated with TP53 mutations and alternative lengthening of telomeres (ALT) | |
Renal cell carcinoma | Global loss of methylation | SETD2 mutations |  | VHL hypermethylation in about 7 % of the tumors†| [36] |
Loss of methylation at non-promoter regions | |||||
One of the tumor types with the lowest frequency of DNA methylation events | |||||
Lung ADCA (3) | CIMP-high | CDKN2A hypermethylation |  | Associated either with ↑ ploidy, ↑ mutation and the PI subtype or with ↓ ploidy, ↓ mutation rate and the TRU subtype | [39] |
MYC overexpression | |||||
Mutations in chromatin modifiers such as SETD2, ARID1A, SMARCA4†| |||||
Lung SQCC (4) | High | CDKN2A inactivation | Â | Classical expression subtype | [38] |
NFE2L2, KEAP1, PTEN mutations | |||||
Chromosomal instability | |||||
↑ SCNAs | |||||
Low | Â | Â | Primitive expression subtype | ||
Serous ovarian (4) | High | Germline and somatic BRCA1 mutations | Â | More differentiated tumors | [34] |
Better survival | |||||
Low | ↑ TP53 mutation | B | TP53 mutations occur in 90 % of the tumors and are not exclusive for the low methylation group | ||
↑ SCNAs | |||||
BRAC1 hypermethylation | |||||
Poor clinical outcome |