OMIC-10. TRANSCRIPTOMIC ANALYSIS REVEALS SEX DIFFERENCES IN PEDIATRIC BRAIN MECHANISMS. (1st June 2021)

• Record Type: Journal Article
• Authors: Yang, Wei; Lathia, Justin D; Connor, James R; Berens, Michael E; Barnholtz-Sloan, Jill S; Rubin, Joshua B
• Is Part Of: Neuro-oncology. Volume 23(2021)Supplement 1
• Page Start: i39
• Page End: i39
• Publication Date: 2021-06-01
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab090.157
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: A significant male overrepresentation exists in cancer incidence and in cancer-related deaths. This is true in all regions of the world and across the lifespan. We published an analysis of adult glioblastoma transcriptomes in which we identified sex-biased molecular features that distinguished the longest surviving male and female patients. Male GBM was characterized by decreased expression of positive regulators of the cell, while female GBM was characterized by decreased expression of intermediates in integrin signaling. To determine whether similar sex differences exist in pediatric brain tumors (pBTs), we accessed 860 pBT transcriptomes, representing all diagnostic categories and ages through the Children's Brain Tumor Network. Unsupervised Bayesian nearest neighbor analysis of gene expression revealed distinct male and female expression patterns indicating fundamental differences exist in pBTs as a function of sex. Similar to our adult GBM analysis, male pBTs were distinguished from female pBTs by the involvement of cell cycle regulatory pathways. In contrast to adult GBM, female pBTs were characterized by involvement of metabolism and inflammatory/ immunity pathways. Interestingly, these sex differences were also evident in a parallel analysis of 209 of neuroblastoma cases. Focused analysis of the most common malignant pBTs (high-grade glioma, medulloblastoma, and ependymoma) revealed that each disease type exhibited significant sex differences in molecular profile, involving distinct pathways in each tumor type. Together, these data indicate that sex-based differences in molecular mechanisms exist in pBTs, and imply that sex-specific approaches to pBT treatment might yield improved outcomes for all patients.