Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/50996 |
Resumo: | Anal cancer is a rare type of digestive tract disease, which has had a crescent incidence in a number of regions. Carcinomas are most frequently found, with squamous cell carcinoma (SCC) comprising similar to 95% of all anal tumors. The major risk factor for development of this type of tumor is human papillomavirus (HPV) infection. However, previous studies have identified patients with anal cancer that are HPV-/p16-and observed that they have a poorer outcome compared with HPV+/p16+ patients. This suggests that molecular profile may drive anal cancer progression. The aim of the present study was to evaluate the mutational status of two important oncogenes, KRAS and BRAF, in a series of anal cancer lesions. Resected tumors of the anal canal (n=43) were evaluated, nine of these were high-grade squamous intra-epithelial lesion cases (HSIL), 11 were adenocarcinomas, and 23 SCCs. Direct sequencing of KRAS proto-oncogene, GTPase (KRAS; codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (BRAF; codon 600) was performed and associated with patient clinicopathological and molecular features. There was a trend of poorer prognosis of adenocarcinoma compared with HSIL and SCC. Analysis indicated one SCC patient (2.3%) exhibited a KRAS p.G13D mutation, and one adenocarcinoma patient (2.3%) exhibited a BRAF p.V600E mutation. It was observed that, these mutations are rare in anal tumors, and certain patients may be at a disadvantage using targeted therapies based on KRAS and BRAF mutational status. As there is a low mutation percentage in SCCs, adenocarcinomas and HSIL, there may exist other underlying molecular alterations that result in anal cancer development, which require further elucidation. |
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Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumorsanal cancersquamous cell carcinomaadenocarcinomahigh -grade squamous intra -epithelial lesionKRASBRAFScience & TechnologyAnal cancer is a rare type of digestive tract disease, which has had a crescent incidence in a number of regions. Carcinomas are most frequently found, with squamous cell carcinoma (SCC) comprising similar to 95% of all anal tumors. The major risk factor for development of this type of tumor is human papillomavirus (HPV) infection. However, previous studies have identified patients with anal cancer that are HPV-/p16-and observed that they have a poorer outcome compared with HPV+/p16+ patients. This suggests that molecular profile may drive anal cancer progression. The aim of the present study was to evaluate the mutational status of two important oncogenes, KRAS and BRAF, in a series of anal cancer lesions. Resected tumors of the anal canal (n=43) were evaluated, nine of these were high-grade squamous intra-epithelial lesion cases (HSIL), 11 were adenocarcinomas, and 23 SCCs. Direct sequencing of KRAS proto-oncogene, GTPase (KRAS; codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (BRAF; codon 600) was performed and associated with patient clinicopathological and molecular features. There was a trend of poorer prognosis of adenocarcinoma compared with HSIL and SCC. Analysis indicated one SCC patient (2.3%) exhibited a KRAS p.G13D mutation, and one adenocarcinoma patient (2.3%) exhibited a BRAF p.V600E mutation. It was observed that, these mutations are rare in anal tumors, and certain patients may be at a disadvantage using targeted therapies based on KRAS and BRAF mutational status. As there is a low mutation percentage in SCCs, adenocarcinomas and HSIL, there may exist other underlying molecular alterations that result in anal cancer development, which require further elucidation.The present study was partially supported by the São Paulo Research Foundation (grant no. 2010/16795-4 to Dr Adhemar Longatto-Filho) and the Ministério da Ciência e Tecnologia/Financiadora de Estudos e Projetos (grant no. CT-INFRA-PROINFRA 01/2011). Dr Lucas Tadeu Bidinotto received a São Paulo Research Foundation fellow-ship (grant no. 2011/08523-7).info:eu-repo/semantics/publishedVersionSpandidos PublicationsUniversidade do MinhoBidinotto, Lucas TadeuVeo, Carlos A. R.Loaiza, Edgar Antonio AlemánFrança, Alessandra Paulino Santos deLorenzi, Adriana TarlaRosa, Luciana Albina ReisOliveira, Cristina Mendes deLevi, José EduardoScapulatempo-Neto, CristovamLongatto, AdhemarReis, R. M.20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/50996eng1791-29971791-300410.3892/mmr.2016.568427573925https://www.spandidos-publications.com/mmr/14/4/3791info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:34:47Zoai:repositorium.sdum.uminho.pt:1822/50996Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:30:32.053841Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors |
title |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors |
spellingShingle |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors Bidinotto, Lucas Tadeu anal cancer squamous cell carcinoma adenocarcinoma high -grade squamous intra -epithelial lesion KRAS BRAF Science & Technology |
title_short |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors |
title_full |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors |
title_fullStr |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors |
title_full_unstemmed |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors |
title_sort |
Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors |
author |
Bidinotto, Lucas Tadeu |
author_facet |
Bidinotto, Lucas Tadeu Veo, Carlos A. R. Loaiza, Edgar Antonio Alemán França, Alessandra Paulino Santos de Lorenzi, Adriana Tarla Rosa, Luciana Albina Reis Oliveira, Cristina Mendes de Levi, José Eduardo Scapulatempo-Neto, Cristovam Longatto, Adhemar Reis, R. M. |
author_role |
author |
author2 |
Veo, Carlos A. R. Loaiza, Edgar Antonio Alemán França, Alessandra Paulino Santos de Lorenzi, Adriana Tarla Rosa, Luciana Albina Reis Oliveira, Cristina Mendes de Levi, José Eduardo Scapulatempo-Neto, Cristovam Longatto, Adhemar Reis, R. M. |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Bidinotto, Lucas Tadeu Veo, Carlos A. R. Loaiza, Edgar Antonio Alemán França, Alessandra Paulino Santos de Lorenzi, Adriana Tarla Rosa, Luciana Albina Reis Oliveira, Cristina Mendes de Levi, José Eduardo Scapulatempo-Neto, Cristovam Longatto, Adhemar Reis, R. M. |
dc.subject.por.fl_str_mv |
anal cancer squamous cell carcinoma adenocarcinoma high -grade squamous intra -epithelial lesion KRAS BRAF Science & Technology |
topic |
anal cancer squamous cell carcinoma adenocarcinoma high -grade squamous intra -epithelial lesion KRAS BRAF Science & Technology |
description |
Anal cancer is a rare type of digestive tract disease, which has had a crescent incidence in a number of regions. Carcinomas are most frequently found, with squamous cell carcinoma (SCC) comprising similar to 95% of all anal tumors. The major risk factor for development of this type of tumor is human papillomavirus (HPV) infection. However, previous studies have identified patients with anal cancer that are HPV-/p16-and observed that they have a poorer outcome compared with HPV+/p16+ patients. This suggests that molecular profile may drive anal cancer progression. The aim of the present study was to evaluate the mutational status of two important oncogenes, KRAS and BRAF, in a series of anal cancer lesions. Resected tumors of the anal canal (n=43) were evaluated, nine of these were high-grade squamous intra-epithelial lesion cases (HSIL), 11 were adenocarcinomas, and 23 SCCs. Direct sequencing of KRAS proto-oncogene, GTPase (KRAS; codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (BRAF; codon 600) was performed and associated with patient clinicopathological and molecular features. There was a trend of poorer prognosis of adenocarcinoma compared with HSIL and SCC. Analysis indicated one SCC patient (2.3%) exhibited a KRAS p.G13D mutation, and one adenocarcinoma patient (2.3%) exhibited a BRAF p.V600E mutation. It was observed that, these mutations are rare in anal tumors, and certain patients may be at a disadvantage using targeted therapies based on KRAS and BRAF mutational status. As there is a low mutation percentage in SCCs, adenocarcinomas and HSIL, there may exist other underlying molecular alterations that result in anal cancer development, which require further elucidation. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016 2016-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/50996 |
url |
http://hdl.handle.net/1822/50996 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1791-2997 1791-3004 10.3892/mmr.2016.5684 27573925 https://www.spandidos-publications.com/mmr/14/4/3791 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Spandidos Publications |
publisher.none.fl_str_mv |
Spandidos Publications |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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