Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors

Detalhes bibliográficos
Autor(a) principal: Bidinotto, Lucas Tadeu
Data de Publicação: 2016
Outros Autores: 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.
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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spelling 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
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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