Kartheuser A, West S, Walon C, Curtis A, Hamzehloei T, Lannoy N, Michiels G, Smaers M, Chapman P, Burn J
Service de Chirurgie de l'Appareil Digestif, Cliniques Universitaires Saint-Luc, (U.C.L.) Bruxelles.
Acta Gastroenterol Belg. 1995 Sep-Dec;58(5-6):433-51.
Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disease that predisposes to colorectal cancer and is characterized by the presence of hundreds to thousands of adenomas covering the colon and rectum. Mapping of the FAP locus to 5q21-q22 by linkage studies in families ultimately allowed the identification of the APC (Adenomatous Polyposis Coli) gene itself. The APC gene comprises 15 exons with a 9 kilobase RNA transcript and a 312 kilodalton final protein product. This discovery transformed the diagnosis of FAP and offered direct identification of defective gene carriers by mutation screening. Currently used techniques have been successful in detecting mutations in 15 to 67 percent of patients. To date, at least 136 different mutations have been described in 301 unrelated FAP patients, most of which (98%) are translation terminating mutations leading to a truncated final protein product. Promising applications or development of novel procedures, like the protein truncation test (PTT), are under way for the remaining FAP patients. With the exception of the description of a critical boundary in exon 9 for the presence or absence of CHRPE, there are no clear genotype-phenotype relationships, but mutations located in the 5' half of exon 15 seem to lead to a more severe phenotype. Very little is know about the APC protein product function. The APC protein could be involved in cell-to-cell signalling and/or cell adhesion functions. The APC gene is a tumour suppressor gene involved in early stages of sporadic colorectal carcinogenesis. Further understanding of the APC gene function may define a rational approach for early detection, prevention strategies, assessment of prognosis and treatment of colorectal cancer. In this regard, animal models of FAP, like the MIN (Multiple Intestinal Neoplasia) mouse or the APC 1638 mouse, are promising and powerful tools.
家族性腺瘤性息肉病（FAP）是一种常染色体显性遗传病，易患结直肠癌，其特征是结肠和直肠上存在数百至数千个腺瘤。通过对家族进行连锁研究，将FAP基因座定位到5q21 - q22，最终鉴定出了APC（腺瘤性息肉病 coli）基因本身。APC基因由15个外显子组成，有一个9千碱基的RNA转录本和一个312千道尔顿的最终蛋白质产物。这一发现改变了FAP的诊断方式，并通过突变筛查直接鉴定出有缺陷基因的携带者。目前使用的技术已成功检测出15%至67%患者的突变。迄今为止，在301名无亲缘关系的FAP患者中已描述了至少136种不同的突变，其中大多数（98%）是导致最终蛋白质产物截短的翻译终止突变。对于其余FAP患者，正在开展如蛋白质截短试验（PTT）等有前景的新方法应用或开发。除了描述外显子9中有无CHRPE的关键界限外，目前尚无明确的基因型 - 表型关系，但位于外显子15 5' 端的突变似乎会导致更严重的表型。对APC蛋白质产物的功能了解甚少。APC蛋白可能参与细胞间信号传导和/或细胞黏附功能。APC基因是一种参与散发性结直肠癌发生早期阶段的肿瘤抑制基因。进一步了解APC基因功能可能会为结直肠癌的早期检测、预防策略、预后评估和治疗确定一种合理的方法。在这方面，FAP的动物模型，如MIN（多发性肠道肿瘤）小鼠或APC 1638小鼠，是很有前景且强大的工具。
