Genomic and Transcriptomic Profiling of Brain Metastases

Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcri...

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Autores principales:	Christopher P. Wardell, Emilie Darrigues, Annick De Loose, Madison P. Lee, Murat Gokden, Issam Makhoul, Alan J. Tackett, Analiz Rodriguez
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bioinformatics genomics transcriptomics brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d591e78b2b614af4abc722ff1c15d4d9
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spelling	oai:doaj.org-article:d591e78b2b614af4abc722ff1c15d4d92021-11-25T17:01:20ZGenomic and Transcriptomic Profiling of Brain Metastases10.3390/cancers132255982072-6694https://doaj.org/article/d591e78b2b614af4abc722ff1c15d4d92021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5598https://doaj.org/toc/2072-6694Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcriptomics and correlate molecular characteristics to clinical parameters. The most common tumor origins for BM were lung (40%) followed by melanoma (21%) and breast (15%). Melanoma and lung BMs contained more deleterious mutations than other subtypes (<i>p</i> < 0.001). Mutational signatures suggested that the bulk of the mutations were gained before metastasis. A novel copy number event centered around the MCL1 gene was found in 75% of all samples, suggesting a broader role in promoting metastasis. Unsupervised hierarchical cluster analysis of transcriptional signatures available in 65 samples based on the hallmarks of cancer revealed four distinct clusters. Melanoma samples formed a distinctive cluster in comparison to other BM subtypes. Characteristics of molecular profiles did not correlate with survival. However, patients with self-identified black race or those who did not receive radiation correlated with poor survival. These data identify potential new drivers of brain metastatic progression. Our data also suggest further investigation of sociodemographic and clinical features is needed in BM cohorts.Christopher P. WardellEmilie DarriguesAnnick De LooseMadison P. LeeMurat GokdenIssam MakhoulAlan J. TackettAnaliz RodriguezMDPI AGarticlebioinformaticsgenomicstranscriptomicsbrain metastasesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5598, p 5598 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bioinformatics genomics transcriptomics brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	bioinformatics genomics transcriptomics brain metastases Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Christopher P. Wardell Emilie Darrigues Annick De Loose Madison P. Lee Murat Gokden Issam Makhoul Alan J. Tackett Analiz Rodriguez Genomic and Transcriptomic Profiling of Brain Metastases
description	Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcriptomics and correlate molecular characteristics to clinical parameters. The most common tumor origins for BM were lung (40%) followed by melanoma (21%) and breast (15%). Melanoma and lung BMs contained more deleterious mutations than other subtypes (<i>p</i> < 0.001). Mutational signatures suggested that the bulk of the mutations were gained before metastasis. A novel copy number event centered around the MCL1 gene was found in 75% of all samples, suggesting a broader role in promoting metastasis. Unsupervised hierarchical cluster analysis of transcriptional signatures available in 65 samples based on the hallmarks of cancer revealed four distinct clusters. Melanoma samples formed a distinctive cluster in comparison to other BM subtypes. Characteristics of molecular profiles did not correlate with survival. However, patients with self-identified black race or those who did not receive radiation correlated with poor survival. These data identify potential new drivers of brain metastatic progression. Our data also suggest further investigation of sociodemographic and clinical features is needed in BM cohorts.
format	article
author	Christopher P. Wardell Emilie Darrigues Annick De Loose Madison P. Lee Murat Gokden Issam Makhoul Alan J. Tackett Analiz Rodriguez
author_facet	Christopher P. Wardell Emilie Darrigues Annick De Loose Madison P. Lee Murat Gokden Issam Makhoul Alan J. Tackett Analiz Rodriguez
author_sort	Christopher P. Wardell
title	Genomic and Transcriptomic Profiling of Brain Metastases
title_short	Genomic and Transcriptomic Profiling of Brain Metastases
title_full	Genomic and Transcriptomic Profiling of Brain Metastases
title_fullStr	Genomic and Transcriptomic Profiling of Brain Metastases
title_full_unstemmed	Genomic and Transcriptomic Profiling of Brain Metastases
title_sort	genomic and transcriptomic profiling of brain metastases
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d591e78b2b614af4abc722ff1c15d4d9
work_keys_str_mv	AT christopherpwardell genomicandtranscriptomicprofilingofbrainmetastases AT emiliedarrigues genomicandtranscriptomicprofilingofbrainmetastases AT annickdeloose genomicandtranscriptomicprofilingofbrainmetastases AT madisonplee genomicandtranscriptomicprofilingofbrainmetastases AT muratgokden genomicandtranscriptomicprofilingofbrainmetastases AT issammakhoul genomicandtranscriptomicprofilingofbrainmetastases AT alanjtackett genomicandtranscriptomicprofilingofbrainmetastases AT analizrodriguez genomicandtranscriptomicprofilingofbrainmetastases
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Genomic and Transcriptomic Profiling of Brain Metastases

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