Sex difference of mutation clonality in diffuse glioma evolution

Area of Science:

• Genomics
• Cancer Biology
• Neuro-oncology

Background:

• Sex differences in glioma incidence and outcomes are known but poorly understood.
• Cancer evolution is thought to be influenced by sex-linked factors.

Purpose of the Study:

• To investigate sex differences in mutation clonality within diffuse gliomas.
• To analyze the timing and clonal status of mutations in approximately 600 gliomas from The Cancer Genome Atlas (TCGA).

Main Methods:

• Utilized an integrated framework to analyze mutation timing and clonal status.
• Examined data from The Cancer Genome Atlas (TCGA) for glioblastomas (GBMs) and low-grade gliomas (LGGs).
• Investigated sex-based differences in mutation clonality across glioma subtypes.

Main Results:

• Female patients exhibited higher overall and subclonal mutation burdens, partly due to X chromosome mutations.
• Identified sex-biased clonality in known drivers like CDH18 and ATRX.
• Observed subtype-specific clonal tendencies and pathway-biased mutations (MAPK in females with GBM, RTK in males with LGG).

Conclusions:

• Diffuse gliomas display sex-biased mutation clonality, including subclonal mutation numbers and gene mutation tendencies.
• Sex should be considered a significant factor for enhancing glioma therapy and clinical management.