Genomic landscape of gliosarcoma: distinguishing features and targetable alterations

Abstract Gliosarcoma is an aggressive brain tumor with histologic features of glioblastoma (GBM) and soft tissue sarcoma. Despite its poor prognosis, its rarity has precluded analysis of its underlying biology. We used a multi-center database to characterize the genomic landscape of gliosarcoma. Seq...

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Autores principales:	Mark M. Zaki, Leila A. Mashouf, Eleanor Woodward, Pinky Langat, Saksham Gupta, Ian F. Dunn, Patrick Y. Wen, Brian V. Nahed, Wenya Linda Bi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96cc0fb61d1e4e1ca5fa1c4476a3bcc7
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spelling	oai:doaj.org-article:96cc0fb61d1e4e1ca5fa1c4476a3bcc72021-12-02T17:19:14ZGenomic landscape of gliosarcoma: distinguishing features and targetable alterations10.1038/s41598-021-97454-62045-2322https://doaj.org/article/96cc0fb61d1e4e1ca5fa1c4476a3bcc72021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97454-6https://doaj.org/toc/2045-2322Abstract Gliosarcoma is an aggressive brain tumor with histologic features of glioblastoma (GBM) and soft tissue sarcoma. Despite its poor prognosis, its rarity has precluded analysis of its underlying biology. We used a multi-center database to characterize the genomic landscape of gliosarcoma. Sequencing data was obtained from 35 gliosarcoma patients from Genomics Evidence Neoplasia Information Exchange (GENIE) 5.0, a database curated by the American Association of Cancer Research (AACR). We analyzed genomic alterations in gliosarcomas and compared them to GBM (n = 1,449) and soft tissue sarcoma (n = 1,042). 30 samples were included (37% female, median age 59 [IQR: 49–64]). Nineteen common genes were identified in gliosarcoma, defined as those altered in > 5% of samples, including TERT Promoter (92%), PTEN (66%), and TP53 (60%). Of the 19 common genes in gliosarcoma, 6 were also common in both GBM and soft tissue sarcoma, 4 in GBM alone, 0 in soft tissue sarcoma alone, and 9 were more distinct to gliosarcoma. Of these, BRAF harbored an OncoKB level 1 designation, indicating its status as a predictive biomarker of response to an FDA-approved drug in certain cancers. EGFR, CDKN2A, NF1, and PTEN harbored level 4 designations in solid tumors, indicating biological evidence of these biomarkers predicting a drug-response. Gliosarcoma contains molecular features that overlap GBM and soft tissue sarcoma, as well as its own distinct genomic signatures. This may play a role in disease classification and inclusion criteria for clinical trials. Gliosarcoma mutations with potential therapeutic indications include BRAF, EGFR, CDKN2A, NF1, and PTEN.Mark M. ZakiLeila A. MashoufEleanor WoodwardPinky LangatSaksham GuptaIan F. DunnPatrick Y. WenBrian V. NahedWenya Linda BiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mark M. Zaki Leila A. Mashouf Eleanor Woodward Pinky Langat Saksham Gupta Ian F. Dunn Patrick Y. Wen Brian V. Nahed Wenya Linda Bi Genomic landscape of gliosarcoma: distinguishing features and targetable alterations
description	Abstract Gliosarcoma is an aggressive brain tumor with histologic features of glioblastoma (GBM) and soft tissue sarcoma. Despite its poor prognosis, its rarity has precluded analysis of its underlying biology. We used a multi-center database to characterize the genomic landscape of gliosarcoma. Sequencing data was obtained from 35 gliosarcoma patients from Genomics Evidence Neoplasia Information Exchange (GENIE) 5.0, a database curated by the American Association of Cancer Research (AACR). We analyzed genomic alterations in gliosarcomas and compared them to GBM (n = 1,449) and soft tissue sarcoma (n = 1,042). 30 samples were included (37% female, median age 59 [IQR: 49–64]). Nineteen common genes were identified in gliosarcoma, defined as those altered in > 5% of samples, including TERT Promoter (92%), PTEN (66%), and TP53 (60%). Of the 19 common genes in gliosarcoma, 6 were also common in both GBM and soft tissue sarcoma, 4 in GBM alone, 0 in soft tissue sarcoma alone, and 9 were more distinct to gliosarcoma. Of these, BRAF harbored an OncoKB level 1 designation, indicating its status as a predictive biomarker of response to an FDA-approved drug in certain cancers. EGFR, CDKN2A, NF1, and PTEN harbored level 4 designations in solid tumors, indicating biological evidence of these biomarkers predicting a drug-response. Gliosarcoma contains molecular features that overlap GBM and soft tissue sarcoma, as well as its own distinct genomic signatures. This may play a role in disease classification and inclusion criteria for clinical trials. Gliosarcoma mutations with potential therapeutic indications include BRAF, EGFR, CDKN2A, NF1, and PTEN.
format	article
author	Mark M. Zaki Leila A. Mashouf Eleanor Woodward Pinky Langat Saksham Gupta Ian F. Dunn Patrick Y. Wen Brian V. Nahed Wenya Linda Bi
author_facet	Mark M. Zaki Leila A. Mashouf Eleanor Woodward Pinky Langat Saksham Gupta Ian F. Dunn Patrick Y. Wen Brian V. Nahed Wenya Linda Bi
author_sort	Mark M. Zaki
title	Genomic landscape of gliosarcoma: distinguishing features and targetable alterations
title_short	Genomic landscape of gliosarcoma: distinguishing features and targetable alterations
title_full	Genomic landscape of gliosarcoma: distinguishing features and targetable alterations
title_fullStr	Genomic landscape of gliosarcoma: distinguishing features and targetable alterations
title_full_unstemmed	Genomic landscape of gliosarcoma: distinguishing features and targetable alterations
title_sort	genomic landscape of gliosarcoma: distinguishing features and targetable alterations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/96cc0fb61d1e4e1ca5fa1c4476a3bcc7
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Genomic landscape of gliosarcoma: distinguishing features and targetable alterations

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