Cargando…

Global molecular alterations involving recurrence or progression of pediatric brain tumors

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 progressi...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Fengju, Chandrashekar, Darshan S., Scheurer, Michael E., Varambally, Sooryanarayana, Creighton, Chad J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649620/
https://www.ncbi.nlm.nih.gov/pubmed/34864569
http://dx.doi.org/10.1016/j.neo.2021.11.014
_version_ 1784611038254071808
author Chen, Fengju
Chandrashekar, Darshan S.
Scheurer, Michael E.
Varambally, Sooryanarayana
Creighton, Chad J.
author_facet Chen, Fengju
Chandrashekar, Darshan S.
Scheurer, Michael E.
Varambally, Sooryanarayana
Creighton, Chad J.
author_sort Chen, Fengju
collection PubMed
description 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<0.001, and these genes could predict patient outcomes in an independent set of pediatric brain tumors. Gene transcript-level associations with recurrence or progression were enriched for protein-level associations. There was a significant overlap in results from pediatric brain tumors and results from adult brain tumors from The Cancer Genome Atlas. Unsupervised analysis defined five subsets of recurrent or progressive tumors, with differences in gene expression and overall patient survival. 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.
format Online
Article
Text
id pubmed-8649620
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Neoplasia Press
record_format MEDLINE/PubMed
spelling pubmed-86496202021-12-21 Global molecular alterations involving recurrence or progression of pediatric brain tumors Chen, Fengju Chandrashekar, Darshan S. Scheurer, Michael E. Varambally, Sooryanarayana Creighton, Chad J. Neoplasia Original article 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<0.001, and these genes could predict patient outcomes in an independent set of pediatric brain tumors. Gene transcript-level associations with recurrence or progression were enriched for protein-level associations. There was a significant overlap in results from pediatric brain tumors and results from adult brain tumors from The Cancer Genome Atlas. Unsupervised analysis defined five subsets of recurrent or progressive tumors, with differences in gene expression and overall patient survival. 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. Neoplasia Press 2021-12-03 /pmc/articles/PMC8649620/ /pubmed/34864569 http://dx.doi.org/10.1016/j.neo.2021.11.014 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original article
Chen, Fengju
Chandrashekar, Darshan S.
Scheurer, Michael E.
Varambally, Sooryanarayana
Creighton, Chad J.
Global molecular alterations involving recurrence or progression of pediatric brain tumors
title Global molecular alterations involving recurrence or progression of pediatric brain tumors
title_full Global molecular alterations involving recurrence or progression of pediatric brain tumors
title_fullStr Global molecular alterations involving recurrence or progression of pediatric brain tumors
title_full_unstemmed Global molecular alterations involving recurrence or progression of pediatric brain tumors
title_short Global molecular alterations involving recurrence or progression of pediatric brain tumors
title_sort global molecular alterations involving recurrence or progression of pediatric brain tumors
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649620/
https://www.ncbi.nlm.nih.gov/pubmed/34864569
http://dx.doi.org/10.1016/j.neo.2021.11.014
work_keys_str_mv AT chenfengju globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors
AT chandrashekardarshans globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors
AT scheurermichaele globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors
AT varamballysooryanarayana globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors
AT creightonchadj globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors