Nagase H, Nakamura Y
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Hum Mutat. 1993;2(6):425-34. doi: 10.1002/humu.1380020602.
Several investigators have reported germline mutations of the APC gene in patients with familial adenomatous polyposis (FAP) as well as somatic mutations in tumors developed in digestive organs (stomach, pancreas, colon, and rectum). Those results provide evidence that inactivation of the APC gene plays a significant role in FAP and in sporadic tumors of these tissues. APC mutations have led to some interesting observations. First, the great majority of the mutations found to date would result in truncation of the APC product. Second, almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region called MCR (mutation cluster region). Third, most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. Fourth, the location of germ-line mutations tends to correlate with the number of colorectal polyps in FAP patients. Furthermore, inactivation of both alleles of the APC gene seems to be required as an early event to develop most of adenomas and carcinomas in the colon and rectum as well as some of those in the stomach.
几位研究者报告了家族性腺瘤性息肉病（FAP）患者中APC基因的种系突变，以及在消化器官（胃、胰腺、结肠和直肠）中发生的肿瘤中的体细胞突变。这些结果证明，APC基因的失活在FAP以及这些组织的散发性肿瘤中起重要作用。APC突变引发了一些有趣的发现。首先，迄今为止发现的绝大多数突变会导致APC产物截短。其次，几乎所有突变都发生在编码序列的前半部分，并且结肠直肠肿瘤中的体细胞突变进一步聚集在一个称为MCR（突变簇区域）的特定区域。第三，APC基因中大多数已鉴定的点突变是从胞嘧啶到其他核苷酸的转换。第四，种系突变的位置往往与FAP患者的结肠直肠息肉数量相关。此外，APC基因两个等位基因的失活似乎是结肠和直肠中大多数腺瘤和癌以及胃中一些腺瘤和癌发生的早期必要事件。
