Illumina Infinium HumanMethylation450 BeadChip (HM450)

Overview

The Illumina Infinium HumanMethylation450 BeadChip (HM450) is a genome-wide DNA methylation array covering approximately 450,000 CpG loci distributed across promoters, gene bodies, enhancers, and intergenic regions. It uses bisulfite conversion followed by two-color fluorescent hybridization, reporting beta values for each probe. The HM450 was the primary methylation platform used in TCGA pan-cancer studies and offers substantially higher CpG coverage than its predecessor HM27.

Used by

  • Applied to 76 GBM samples (113 in re-analysis) as part of TCGA GBM 2013 multi-platform methylation analysis; contributed to the six-class methylation model (M1–M6); identified G-CIMP classification using higher-density data to refine the HM27-derived findings PMID:24120142
  • Illumina HumanMethylation450 (HM450) array applied to 131 TCGA bladder carcinoma samples; identified a CIMP subgroup in 34% of tumors; smoking pack-years was the only significant predictor of CIMP phenotype on multivariate regression PMID:24476821
  • Used as one of five molecular platforms in the TCGA HCC integrated characterisation (196 patients) for DNA methylation profiling alongside WES, RNA-seq, miRNA-seq, and RPPA PMID:24798001
  • DNA methylation profiling of 295 gastric adenocarcinomas (stad_tcga_pub) by HM450 array identified EBV-specific extreme CIMP, MLH1 promoter hypermethylation driving MSI, and CDKN2A silencing in EBV-positive tumors PMID:25079317
  • HM450 methylation profiling of 230 lung adenocarcinomas (luad_tcga_pub) defined CIMP-H and CIMP-L clusters; CIMP-H tumors showed hypermethylation of WNT pathway genes, CDKN2A, and HOXA9/HOXD13, and were associated with MYC overexpression PMID:25079552
  • Used to profile DNA methylation at ~450,000 loci in 66 ChRCC tumors; identified >64,000 differentially methylated loci vs ccRCC and CDKN2A epigenetic silencing in 4 cases. PMID:25155756
  • Applied to TCGA HNSC (n=279); revealed DNA hypomethylation associated with NSD1 loss-of-function mutations, defining the atypical/classical mRNA subtype enrichment and connecting histone methylation to DNA methylation states PMID:25631445
  • Used in the TCGA breast cancer ILC/IDC study (n=817) for genome-wide DNA methylation profiling; data confirmed absence of CDH1 promoter hypermethylation in ILC, contradicting older MSP-based reports PMID:26451490
  • Profiled 39 primary neuroblastomas to characterize chromatin state at the TERT locus; CpG methylation increased in rearranged and MYCN-amplified tumors, particularly at a CpG near the TERT core promoter linked to disabled repression PMID:26466568
  • Profiled DNA methylation in 333 primary prostate adenocarcinomas (TCGA); identified four epigenetic clusters and a CIMP-like IDH1 R132-mutant subgroup with greater genome-wide hypermethylation than IDH1-mutant GBM or AML PMID:26544944.
  • Used for DNA methylation profiling of 516 LGG and 129 GBM samples in the TCGA pan-glioma study; merged with HM27 data to define six pan-glioma methylation clusters (LGm1–6); methylation subtype was an independent prognostic predictor (C-index 0.836 with age + grade) PMID:26824661
  • Illumina HumanMethylation450 BeadChip applied on day 0 and day 10 of cycle 1 in AML/MDS patients on decitabine; global CpG methylcytosine reduction was similar between responders and non-responders and not predictive of decitabine response. PMID:27959731
  • Illumina HumanMethylation450 (HM450) arrays profiled DNA methylation of 164 oesophageal carcinomas and gastric cancers; revealed a proximal-to-distal hypermethylation gradient in GEA-CIN tumors and defined the hypermethylated cluster enriched in EAC PMID:28052061.
  • Profiled all 412 BLCA tumors; identified 158 epigenetically silenced genes and a hypomethylation cluster corresponding to the luminal-papillary subtype (enriched FGFR3 mutations, better survival) PMID:28988769
  • Applied to 206 TCGA sarcomas; combined SCNA + methylation clustering defined DDLPS prognostic subtypes (K3 vs K1+K2, p=0.001); hypermethylation alone (Meth2) yielded HR=4.4 (p=0.002) in DDLPS PMID:29100075

Notes

  • Covers ~450,000 CpG sites including CpG islands, shores, shelves, and open sea regions.
  • The HM450 has been a standard for TCGA methylation profiles across tumor types; the EPIC array (~850K probes) is its successor.
  • Beta values from HM450 enabled identification of distinct methylation subclasses (M1–M6) with clinical and molecular correlates in GBM.

Sources

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This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

This page was processed by crosslinker on 2026-05-14. - PMID:25079552

This page was processed by crosslinker on 2026-05-14. - PMID:25155756

This page was processed by crosslinker on 2026-05-14. - PMID:25631445

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

This page was processed by crosslinker on 2026-05-14. - PMID:26466568

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by crosslinker on 2026-05-14. - PMID:26824661

This page was processed by entity-page-writer on 2026-05-15. - PMID:27959731

This page was processed by entity-page-writer on 2026-05-15. - PMID:28052061

This page was processed by wiki-cli on 2026-05-14. - PMID:28988769

This page was processed by entity-page-writer on 2026-05-15. - PMID:29100075

This page was processed by entity-page-writer on 2026-05-15.