title: Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors.
abstract: 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 ~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.
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Lucas Tadeu
authors: LT
authors: Bidinotto
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Carlos A R
authors: CA
authors: Véo
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Edgar Aleman
authors: EA
authors: Loaiza
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Alessandra Paulino Santos
authors: AP
authors: De França
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Adriana Tarla
authors: AT
authors: Lorenzi
authors: Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, São Paulo 05403 000, Brazil.
authors: Luciana Albina Reis
authors: LA
authors: Rosa
authors: Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, São Paulo 05403 000, Brazil.
authors: Cristina Mendes
authors: CM
authors: De Oliveira
authors: Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, São Paulo 05403 000, Brazil.
authors: José Eduardo
authors: JE
authors: Levi
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Cristovam
authors: C
authors: Scapulatempo-Neto
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Adhemar
authors: A
authors: Longatto-Filho
authors: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784 400, Brazil.
authors: Rui Manuel
authors: RM
authors: Reis
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D001003:Anal Canal / Q000378:metabolism / Q000473:pathology*; D001005:Anus Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D001938:Brazil / Q000453:epidemiology; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D030361:Papillomavirus Infections / Q000150:complications; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)