Department of Medical Genetics, Medical Science Faculty, University of Campinas, Cidade Universitária, Campinas, SP 13081-970, Brazil.
Oncol Rep. 2013 Nov;30(5):2081-8. doi: 10.3892/or.2013.2681. Epub 2013 Aug 21.
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.
腺瘤性结肠息肉病（APC）种系突变是家族性腺瘤性息肉病（FAP）发生的原因。体细胞突变导致腺瘤的恶性转化。在这种情况下，考虑到 APC 种系突变在 FAP 中的重要性，我们旨在鉴定 APC 种系突变。在本研究中，纳入了 20 名 FAP 患者。使用测序确定 APC 种系突变，并将突变与临床标志物（性别、诊断时年龄、吸烟习惯、TNM 分期、Astler-Coller 分期、腺癌分化程度）进行比较。使用 SPSS 程序进行数据比较，Fisher 确切检验和 χ2 检验，α=0.05。根据我们样本中的主要结果，确定了 16 个具有有害突变的等位基因（80%的患者），而 7 个（35%）患者没有有害突变。无义突变（45%的患者）和移码突变（20%的患者）占主导地位。在我们研究中考虑的临床变量与鉴定的 APC 种系突变之间没有统计学意义。只有 TNM 分期与有害突变的存在相关。与未鉴定出有害突变的患者相比，具有有害突变的患者的 OR 为 0.086（IC=0.001-0.984）；TNM 分期 I+II 与 III+IV。在这种情况下，作为结论，我们证明了 FAP 中 APC 种系突变的分子异质性以及在考虑到分析的混合人群时在巴西人群中进行分子诊断的困难。
