Global molecular alterations involving recurrence or progression of pediatric brain tumors.

TitleGlobal molecular alterations involving recurrence or progression of pediatric brain tumors.
Publication TypeJournal Article
Year of Publication2022
AuthorsChen, F, Chandrashekar, DS, Scheurer, ME, Varambally, S, Creighton, CJ
JournalNeoplasia
Volume24
Issue1
Pagination22-33
Date Published2022 Jan
ISSN1476-5586
KeywordsBiomarkers, Tumor, Brain Neoplasms, Child, Computational Biology, Databases, Genetic, Disease Progression, Disease Susceptibility, Exome Sequencing, Gene Expression Profiling, Genetic Predisposition to Disease, Humans, Mutation, Recurrence, Transcriptome
Abstract

BACKGROUND: We aimed to identify molecular changes in recurrent or progressive pediatric brain tumors, as compared to the corresponding initial tumors from the same patients, using genomic, transcriptomic, and proteomic data from a unique and large cohort of 55 patients and 63 recurrent or progressive tumors from the Children's Brain Tumor Tissue Consortium, representing various histologic types.

METHODS: We carried out paired analyses for each gene between recurrent/progressive and initial tumor groups, using RNA-sequencing and mass spectrometry-based proteomic data. By whole-genome sequencing (WGS) analysis, we also examined somatic DNA events for a set of cancer-associated genes.

RESULTS: Of 44 patients examined by WGS, 35 involved at least one cancer-associated gene with a somatic alteration event in a recurrent or progressive tumor that was not present in the initial tumor, including genes NF1, CDKN2A, CCND2, EGFR, and MYCN. By paired analysis, 68 mRNA transcripts were differentially expressed in recurrent/progressive tumors with p

CONCLUSIONS: Our study uncovers genes showing consistent expression differences in recurrent or progressive tumors. These genes may provide molecular clues as to processes or pathways underlying more aggressive pediatric brain tumors.

DOI10.1016/j.neo.2021.11.014
Alternate JournalNeoplasia
PubMed ID34864569
PubMed Central IDPMC8649620
Grant ListP30 CA125123 / CA / NCI NIH HHS / United States
U54 CA118948 / CA / NCI NIH HHS / United States

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