Sex differences in methylation profiles are apparent in medulloblastoma, particularly among SHH tumors

Medulloblastoma, the most common malignant pediatric brain tumor, displays marked sex differences in prevalence of the four main molecular subgroups: SHH, WNT, Group 3 and Group 4. Males are more frequently diagnosed with SHH, Group 3 and 4 tumors, which have worse prognoses than WNT tumors. Little...

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Bibliographic Details
Published in:Frontiers in oncology 2023-03, Vol.13, p.1113121-1113121
Main Authors: Moss, Rachel M, Sorajja, Natali, Mills, Lauren J, Moertel, Christopher L, Hoang, Thanh T, Spector, Logan G, Largaespada, David A, Williams, Lindsay A
Format: Article
Language:English
Subjects:
medulloblastoma
methylation
Oncology
pediatric and young adult cancer
sex differences
survival
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Summary:Medulloblastoma, the most common malignant pediatric brain tumor, displays marked sex differences in prevalence of the four main molecular subgroups: SHH, WNT, Group 3 and Group 4. Males are more frequently diagnosed with SHH, Group 3 and 4 tumors, which have worse prognoses than WNT tumors. Little is known about sex differences in methylation profiles within subgroups. Using publicly available methylation data (Illumina HumanMethylation450K array), we compared beta values for males versus females. Differentially methylated positions (DMP) by sex within medulloblastoma subgroups were identified on the autosomes. DMPs were mapped to genes and Reactome pathway analysis was run by subgroup. Kaplan-Meier survival curves (Log-Rank p-values) were assessed for each sex within subgroup. was used to investigate the tumor microenvironment using deconvolution to estimate the abundances of immune cell types using DNA methylation data. There were statistically significant differences in sex by medulloblastoma subgroups (chi-squared p-value=0.00004): Group 3 (n=144; 65% male), Group 4 (n=326; 67% male), SHH (n=223; 57% male) and WNT (n=70; 41% male). Females had worse survival than males for SHH (p-value=0.02). DMPs by sex were identified within subgroups: SHH (n=131), Group 4 (n=29), Group 3 (n=19), and WNT (n=16) and validated in an independent dataset. Unsupervised hierarchical clustering showed that sex-DMPs in SHH did not correlate with other tumor attributes. Ten genes with sex DMPs ( , , , , , , , , , and were shared across subgroups. Significant pathways (p
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2023.1113121