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...

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Autores principales:	Fengju Chen, Darshan S. Chandrashekar, Michael E. Scheurer, Sooryanarayana Varambally, Chad J. Creighton
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Recurrence Progression Pediatric brain tumors RNA-sequencing Proteomics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/45707316c97641ce873b1d57d6239e64
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spelling	oai:doaj.org-article:45707316c97641ce873b1d57d6239e642021-12-04T04:33:26ZGlobal molecular alterations involving recurrence or progression of pediatric brain tumors1476-558610.1016/j.neo.2021.11.014https://doaj.org/article/45707316c97641ce873b1d57d6239e642022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1476558621001032https://doaj.org/toc/1476-5586Background: 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.Fengju ChenDarshan S. ChandrashekarMichael E. ScheurerSooryanarayana VaramballyChad J. CreightonElsevierarticleRecurrenceProgressionPediatric brain tumorsRNA-sequencingProteomicsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENNeoplasia: An International Journal for Oncology Research, Vol 24, Iss 1, Pp 22-33 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Recurrence Progression Pediatric brain tumors RNA-sequencing Proteomics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Recurrence Progression Pediatric brain tumors RNA-sequencing Proteomics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Fengju Chen Darshan S. Chandrashekar Michael E. Scheurer Sooryanarayana Varambally Chad J. Creighton Global molecular alterations involving recurrence or progression of pediatric brain tumors
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	article
author	Fengju Chen Darshan S. Chandrashekar Michael E. Scheurer Sooryanarayana Varambally Chad J. Creighton
author_facet	Fengju Chen Darshan S. Chandrashekar Michael E. Scheurer Sooryanarayana Varambally Chad J. Creighton
author_sort	Fengju Chen
title	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_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_sort	global molecular alterations involving recurrence or progression of pediatric brain tumors
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/45707316c97641ce873b1d57d6239e64
work_keys_str_mv	AT fengjuchen globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors AT darshanschandrashekar globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors AT michaelescheurer globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors AT sooryanarayanavarambally globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors AT chadjcreighton globalmolecularalterationsinvolvingrecurrenceorprogressionofpediatricbraintumors
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Global molecular alterations involving recurrence or progression of pediatric brain tumors

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