Mutation profiling of cancer drivers in Brazilian colorectal cancer

Abstract The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite inst...

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Autores principales:	Wellington dos Santos, Thais Sobanski, Ana Carolina de Carvalho, Adriane Feijó Evangelista, Marcus Matsushita, Gustavo Nóriz Berardinelli, Marco Antonio de Oliveira, Rui Manuel Reis, Denise Peixoto Guimarães
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/204103590af1472cbc1cdf906c8e6edf
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spelling	oai:doaj.org-article:204103590af1472cbc1cdf906c8e6edf2021-12-02T15:10:03ZMutation profiling of cancer drivers in Brazilian colorectal cancer10.1038/s41598-019-49611-12045-2322https://doaj.org/article/204103590af1472cbc1cdf906c8e6edf2019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49611-1https://doaj.org/toc/2045-2322Abstract The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite instability (MSI) and genetic ancestry in a series of 91 Brazilian CRC patients. Driver mutations were found in the APC (71.4%), TP53 (56.0%), KRAS (52.7%), PIK3CA (15.4%) and FBXW7 (10.9%) genes. Overall, genes in the MAPK/ERK, PIK3/AKT, NOTCH and receptor tyrosine kinase signaling pathways were mutated in 68.0%, 23.1%, 16.5%, and 15.3% of patients, respectively. MSI was found in 13.3% of tumors, most of which were proximal (52.4%, P< 0.001) and had a high mutation burden. European genetic ancestry was predominant (median of 83.1%), followed by Native American (4.1%), Asian (3.4%) and African (3.2%). NF1 and BRAF mutations were associated with African ancestry, while TP53 and PIK3CA mutations were inversely correlated with Native American ancestry. Our study suggests that Brazilian CRC patients exhibit a mutation profile similar to other populations and identify the most frequently mutated genes, which could be useful in future target therapies and molecular cancer screening strategies.Wellington dos SantosThais SobanskiAna Carolina de CarvalhoAdriane Feijó EvangelistaMarcus MatsushitaGustavo Nóriz BerardinelliMarco Antonio de OliveiraRui Manuel ReisDenise Peixoto GuimarãesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wellington dos Santos Thais Sobanski Ana Carolina de Carvalho Adriane Feijó Evangelista Marcus Matsushita Gustavo Nóriz Berardinelli Marco Antonio de Oliveira Rui Manuel Reis Denise Peixoto Guimarães Mutation profiling of cancer drivers in Brazilian colorectal cancer
description	Abstract The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite instability (MSI) and genetic ancestry in a series of 91 Brazilian CRC patients. Driver mutations were found in the APC (71.4%), TP53 (56.0%), KRAS (52.7%), PIK3CA (15.4%) and FBXW7 (10.9%) genes. Overall, genes in the MAPK/ERK, PIK3/AKT, NOTCH and receptor tyrosine kinase signaling pathways were mutated in 68.0%, 23.1%, 16.5%, and 15.3% of patients, respectively. MSI was found in 13.3% of tumors, most of which were proximal (52.4%, P< 0.001) and had a high mutation burden. European genetic ancestry was predominant (median of 83.1%), followed by Native American (4.1%), Asian (3.4%) and African (3.2%). NF1 and BRAF mutations were associated with African ancestry, while TP53 and PIK3CA mutations were inversely correlated with Native American ancestry. Our study suggests that Brazilian CRC patients exhibit a mutation profile similar to other populations and identify the most frequently mutated genes, which could be useful in future target therapies and molecular cancer screening strategies.
format	article
author	Wellington dos Santos Thais Sobanski Ana Carolina de Carvalho Adriane Feijó Evangelista Marcus Matsushita Gustavo Nóriz Berardinelli Marco Antonio de Oliveira Rui Manuel Reis Denise Peixoto Guimarães
author_facet	Wellington dos Santos Thais Sobanski Ana Carolina de Carvalho Adriane Feijó Evangelista Marcus Matsushita Gustavo Nóriz Berardinelli Marco Antonio de Oliveira Rui Manuel Reis Denise Peixoto Guimarães
author_sort	Wellington dos Santos
title	Mutation profiling of cancer drivers in Brazilian colorectal cancer
title_short	Mutation profiling of cancer drivers in Brazilian colorectal cancer
title_full	Mutation profiling of cancer drivers in Brazilian colorectal cancer
title_fullStr	Mutation profiling of cancer drivers in Brazilian colorectal cancer
title_full_unstemmed	Mutation profiling of cancer drivers in Brazilian colorectal cancer
title_sort	mutation profiling of cancer drivers in brazilian colorectal cancer
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/204103590af1472cbc1cdf906c8e6edf
work_keys_str_mv	AT wellingtondossantos mutationprofilingofcancerdriversinbraziliancolorectalcancer AT thaissobanski mutationprofilingofcancerdriversinbraziliancolorectalcancer AT anacarolinadecarvalho mutationprofilingofcancerdriversinbraziliancolorectalcancer AT adrianefeijoevangelista mutationprofilingofcancerdriversinbraziliancolorectalcancer AT marcusmatsushita mutationprofilingofcancerdriversinbraziliancolorectalcancer AT gustavonorizberardinelli mutationprofilingofcancerdriversinbraziliancolorectalcancer AT marcoantoniodeoliveira mutationprofilingofcancerdriversinbraziliancolorectalcancer AT ruimanuelreis mutationprofilingofcancerdriversinbraziliancolorectalcancer AT denisepeixotoguimaraes mutationprofilingofcancerdriversinbraziliancolorectalcancer
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Mutation profiling of cancer drivers in Brazilian colorectal cancer

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