Navegando por Palavras-chave "Genes de reparo"

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    Estudo das mutações germinativas nos genes de reparo e Epcam em pacientes com suspeita Síndrome de Lynch
    (Universidade Federal de São Paulo (UNIFESP), 2018-01-29) Pimenta, Celia Aparecida Marques [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Oshima, Celina Tizuko Fujiyama; Lima, Fernanda Teresa; http://lattes.cnpq.br/8007052437699905; http://lattes.cnpq.br/0012255593371579; http://lattes.cnpq.br/7314943504526739; http://lattes.cnpq.br/5028766737923753; Universidade Federal de São Paulo (UNIFESP)
    Background: Lynch syndrome (SL) is the most common inherited colorectal cancer (CRC) syndrome, representing 2 to 4% of all cases of CRC, because presenting few polyps is also known as HNPCC (nonpolypoid hereditary colorectal cancer). Most subjects with SL have at least one pathogenic mutation of the MMR (mismatch repair) genes MLH1, MSH2, MSH6 or PMS2. Objectives: Evaluate patients with CRC and gastric cancer (GC) with suspicion of SL by immunohistochemistry and sequencing of DNA repair genes, and EPCAM. Patients and methods: We analyzed 116 medical records of patients with CRC and GC related to SL with at least one of the Bethesda criteria, after an interview with a patient and consultation with a geneticist. An immunohistochemical test and a new generation sequencing (NGS) of repair genes was performed to investigate the expression of the repair proteins, EPCAM and BRAF. Results: Among the 116 patients, 95 were considered eligible. The mean age at diagnosis of CRC or CG in women was 50.7 years and in men 54.03. Regarding the tumor location, 40% presented tumor in the right colon, 60% had a moderately differentiated histological grade. Immunohistochemistry was performed to study the immunoexpression of the repair proteins in 95 samples of tumors tissue and 75.6% had absence of expression in at least 1 of the proteins. Among tumors with some mutations, 74% of the patients were younger than 50 years and 47% of the CRC were on left colon. NGS was performed on 95 blood samples. The MLH1 gene had 13% of pathogenic mutations, MSH2 7%, MSH6 5%, and EPCAM 1%. The number of patients affected by some mutation corresponded to 30% (29/95). Conclusion: The MLH1 gene mutation was the most frequent. The percentage of pathogenic mutations of the EPCAM gene was very rare. Approximately 50% of the patients with absence of expression of the repair genes presented pathogenic mutation at sequencing. This difference reinforces the importance of the sequencing study among patients with altered expression of repair proteins.
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    Polimorfismos em genes de reparo do DNA (XPC, ERCC1, XRCC7) em mulheres com câncer do colo do útero
    (Universidade Federal de São Paulo (UNIFESP), 2010-06-30) Saffar, Issamir Farias [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Estudos demonstram que polimorfismos em genes relacionados ao reparo do DNA estão envolvidos na patogênese de diversas doenças neoplásicas, como o câncer ginecológico, particularmente o câncer do colo do útero. O presente estudo, caso-controle, compara os polimorfismos dos genes XPC, ERCC1 e XRCC7 em 77 mulheres com câncer cervical (70 casos de carcinoma espinocelular e 7 casos de adenocarcinoma do colo do útero) e 73 mulheres saudáveis atendidas no Hospital do Câncer Alfredo Abrão, entre Junho de 2007 e Maio de 2009. No Laboratório de Ginecologia Molecular da EPM-UNIFESP, os polimorfismos desses genes foram detectados pela técnica de reação em cadeia da polimerase seguida da análise do polimorfismo do fragmento de restrição (PCR-RFLP). As distribuições genotípicas dos polimorfismos no grupo de casos e controle estavam em Equilíbrio de Hardy-Weinberg (p>0,05). Pelo teste exato de Fisher as distribuições genotípicas dos polimorfismos (XRCC7 (G-C): GG (11,7%), GC (41,6%) e CC (46,8%) no grupo de casos e GG (20,5%), GC (41,1%) e CC (38,4%) no grupo controle (p=0,31); ERCC1 (C-T): CC (39,0%), CT (51,9%) e TT (9,1%) no grupo de casos e CC (53,4%), CT (38,4%) e TT (8,2%) no grupo controle (p=0,20); XPC (A-C): AA (50,6%), AC (41,6%) e AA (7,8%) no grupo de casos e AA (45,2%), AC (37,0%) e CC (17,8%) no grupo controle, p=0,19) não apresentaram diferença estatística significante. Nossos resultados mostram que os polimorfismos XPC, ERCC1 e XRCC7 não são correlacionados ao risco para desenvolvimento do câncer do colo do útero na população estudada.