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Table S2 from Rates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain

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posted on 2023-04-03, 23:43 authored by Javier Ganz, Eduardo A. Maury, Basheer Becerra, Sara Bizzotto, Ryan N. Doan, Connor J. Kenny, Taehwan Shin, Junho Kim, Zinan Zhou, Keith L. Ligon, Eunjung Alice Lee, Christopher A. Walsh

Supplementary information related to GTEx and BrainVar analyses.

Funding

American Brain Tumor Association (ABTA)

National Cancer Institute (NCI)

United States Department of Health and Human Services

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Harvard/MIT MD-PhD MSTP Program

Biomedical Informatics and Data Science Training Program

Ruth Kirschstein NRSA F31 Fellowship

National Institutes of Health (NIH)

Pediatric Brain Tumor Foundation (PBTF)

Pediatric Low Grade Astrocytoma Foundation (PLGA Foundation)

Suh Kyungbae Foundation

National Institute of Neurological Disorders and Stroke (NINDS)

United States Department of Health and Human Services

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National Institute of Mental Health (NIMH)

United States Department of Health and Human Services

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National Institute on Aging (NIA)

United States Department of Health and Human Services

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Allen Discovery Center - Paul G. Allen Frontiers Group

Howard Hughes Medical Institute (HHMI)

National Human Genome Research Institute (NHGRI)

United States Department of Health and Human Services

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History

ARTICLE ABSTRACT

Although oncogenic mutations have been found in nondiseased, proliferative nonneural tissues, their prevalence in the human brain is unknown. Targeted sequencing of genes implicated in brain tumors in 418 samples derived from 110 individuals of varying ages, without tumor diagnoses, detected oncogenic somatic single-nucleotide variants (sSNV) in 5.4% of the brains, including IDH1R132H. These mutations were largely present in subcortical white matter and enriched in glial cells and, surprisingly, were less common in older individuals. A depletion of high-allele frequency sSNVs representing macroscopic clones with age was replicated by analysis of bulk RNA sequencing data from 1,816 nondiseased brain samples ranging from fetal to old age. We also describe large clonal copy number variants and that sSNVs show mutational signatures resembling those found in gliomas, suggesting that mutational processes of the normal brain drive early glial oncogenesis. This study helps understand the origin and early evolution of brain tumors. In the nondiseased brain, clonal oncogenic mutations are enriched in white matter and are less common in older individuals. We revealed early steps in acquiring oncogenic variants, which are essential to understanding brain tumor origins and building new mutational baselines for diagnostics.This article is highlighted in the In This Issue feature, p. 1

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    Cancer Discovery

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    cancer

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