Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
Gut Liver. 2013 May;7(3):295-302. doi: 10.5009/gnl.2013.7.3.295. Epub 2013 Apr 9.
BACKGROUND/AIMS: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran.
Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months.
Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p<0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p<0.01).
Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease.
背景/目的：我们旨在研究伊朗中部伊斯法罕原发性结直肠癌中 p53 基因的各种突变及其蛋白产物、组织学特征与疾病预后之间的关系。
本研究纳入了 61 例结直肠腺癌患者。通过单链构象多态性和 DNA 测序检测 p53 基因突变。通过免疫组织化学评估蛋白质稳定性。对患者进行了 48 个月的随访。
在 14 例患者（23%）的肿瘤标本中检测到外显子 5 和 6 中的 21 个点突变。其中，81%和 9.5%分别为错义突变和无义突变。在 5 和 6 外显子之间的内含子区还存在两个新的突变。在 11 个突变标本中，鉴定到了蛋白质稳定性和蛋白积累。p53 基因外显子 5 和 6 中的突变类型与蛋白积累之间存在关系。突变的存在与癌症的晚期阶段有关（趋势，p<0.009）。携带突变 p53 基因的患者的生存率明显低于携带野生型 p53 基因的患者（p<0.01）。
伊朗中部结直肠腺癌中 p53 基因外显子 5 和 6 的突变是常见的遗传改变，与疾病预后不良相关。
