title: APC germline mutations in families with familial adenomatous polyposis.
abstract: Adenomatous polyposis coli (APC) germline mutations are responsible for the occurrence of familial adenomatous polyposis (FAP). Somatic mutations lead to malignant transformation of adenomas. In this context, considering the significance of APC germline mutations in FAP, we aimed to identify APC germline mutations. In the present study, 20 FAP patients were enrolled. The determination of APC germline mutations was performed using sequencing, and the mutations were compared with clinical markers (gender, age at diagnosis, smoking habits, TNM stage, Astler‑Coller stage, degree of differentiation of adenocarcinoma). The data were compared using the SPSS program, with the Fisher's exact test and χ2 test, considering α=0.05. According to the main results in our sample, 16 alleles with deleterious mutations (80% of the patients) were identified while 7 (35%) patients had no deleterious mutations. There was a predominance of nonsense (45% of the patients) and frameshift (20% of the patients) mutations. There was no statistical significance between the APC germline mutations identified and the clinical variables considered in our study. Only TNM stage was associated with the presence of deleterious mutations. Patients with deleterious mutations had an OR, 0.086 (IC=0.001-0.984); TNM stage I+II in comparison with III+IV, when compared with the patients with no deleterious mutations identified. In this context, as a conclusion, we demonstrated the molecular heterogeneity of APC germline mutations in FAP and the difficulty to perform molecular diagnostics in a Brazilian population, considering the admixed population analyzed.
authors: Department of Medical Genetics, Medical Science Faculty, University of Campinas, Cidade Universitária, Campinas, SP 13081-970, Brazil.
authors: Lillian Barbosa
authors: LB
authors: De Queiroz Rossanese
authors: Fernando Augusto
authors: FA
authors: De Lima Marson
authors: José Dirceu
authors: JD
authors: Ribeiro
authors: Claudio Saddy Rodrigues
authors: CS
authors: Coy
authors: Carmen Silvia
authors: CS
authors: Bertuzzo
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D001938:Brazil; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D025601:Adenomatous Polyposis Coli Protein