Dataset Information

Genome wide DNA methylation analysis identifies novel molecular subgroups and predicts survival in neuroblastoma.

ABSTRACT:

Background

Neuroblastoma is the most common malignancy in infancy, accounting for 15% of childhood cancer deaths. Outcome for the high-risk disease remains poor. DNA-methylation patterns are significantly altered in all cancer types and can be utilised for disease stratification.

Methods

Genome-wide DNA methylation (n = 223), gene expression (n = 130), genetic/clinical data (n = 213), whole-exome sequencing (n = 130) was derived from the TARGET study. Methylation data were derived from HumanMethylation450 BeadChip arrays. t-SNE was used for the segregation of molecular subgroups. A separate validation cohort of 105 cases was studied.

Results

Five distinct neuroblastoma molecular subgroups were identified, based on genome-wide DNA-methylation patterns, with unique features in each, including three subgroups associated with known prognostic features and two novel subgroups. As expected, Cluster-4 (infant diagnosis) had significantly better 5-year progression-free survival (PFS) than the four other clusters. However, in addition, the molecular subgrouping identified multiple patient subsets with highly increased risk, most notably infant patients that do not map to Cluster-4 (PFS 50% vs 80% for Cluster-4 infants, P = 0.005), and allowed identification of subgroup-specific methylation differences that may reflect important biological differences within neuroblastoma.

Conclusions

Methylation-based clustering of neuroblastoma reveals novel molecular subgroups, with distinct molecular/clinical characteristics and identifies a subgroup of higher-risk infant patients.

SUBMITTER: Lalchungnunga H

PROVIDER: S-EPMC9681858 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Genome wide DNA methylation analysis identifies novel molecular subgroups and predicts survival in neuroblastoma.

Lalchungnunga H H Hao Wen W Maris John M JM Asgharzadeh Shahab S Henrich Kai-Oliver KO Westermann Frank F Tweddle Deborah A DA Schwalbe Edward C EC Strathdee Gordon G

British journal of cancer 20220929 11

<h4>Background</h4>Neuroblastoma is the most common malignancy in infancy, accounting for 15% of childhood cancer deaths. Outcome for the high-risk disease remains poor. DNA-methylation patterns are significantly altered in all cancer types and can be utilised for disease stratification.<h4>Methods</h4>Genome-wide DNA methylation (n = 223), gene expression (n = 130), genetic/clinical data (n = 213), whole-exome sequencing (n = 130) was derived from the TARGET study. Methylation data were derived ...[more]

PMID: 36175618

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Project description:BackgroundMeasuring the DNA methylome may offer the opportunity to identify novel disease biomarkers and insights into disease mechanisms. Although aberrant DNA methylation has been investigated in many human cancers and precancerous lesions, the DNA methylation landscape of gastric cardiac intestinal metaplasia (IM) remains unknown. Therefore, we aimed to investigate the genome-wide DNA methylation landscape and to search for potential epigenetic biomarkers of gastric cardiac IM.MethodsHistopathologic profiling was performed on a total of 118 gastric cardiac biopsies from cancer-free individuals. Genome-wide DNA methylation analysis was performed on 11 gastric cardiac mucosal biopsies (IM = 7; normal = 4) using Illumina 850K microarrays. Transcriptional relevance of any candidate epigenetic biomarker was validated by qRT-PCR.ResultsThe detection rate of gastric cardiac IM was 23% (27/118) in cancer-free individuals. Genome-wide DNA methylation profiling showed a global decrease in methylation in IM compared with normal tissues (median methylation = 0.64 and 0.70 for gastric cardiac IM and normal tissues, respectively). Differential methylation analysis between gastric cardiac IM and normal tissues identified 38,237 differentially methylated probes (DMPs) with a majority of sites showing hypermethylation in IM compared with normal tissues (56.3% vs. 43.7%). Subsequent analysis revealed a significant enrichment of hypermethylated DMPs in promoter and CpG islands (p < 0.001 for both, Pearson χ2 test). For DMPs located in promoter CpG islands showing extreme hypermethylation, the candidate gene with the largest number of DMPs (n = 7) was mapped to HOXA5. Accordingly, mRNA expression of HOXA5 was significantly reduced in IM compared to normal tissue.ConclusionsOur results suggest the implication of alterations in DNA methylation in gastric cardiac IM and highlight that HOXA5 hypermethylation may be a promising epigenetic biomarker, emphasizing the role of aberrant HOXA5 expression in the pathogenesis of gastric cardiac IM.

Dataset Information

Genome wide DNA methylation analysis identifies novel molecular subgroups and predicts survival in neuroblastoma.

Background

Methods

Results

Conclusions

Publications

Genome wide DNA methylation analysis identifies novel molecular subgroups and predicts survival in neuroblastoma.

Similar Datasets

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