Yamaguchi K, Chijiiwa K, Noshiro H, Torata N, Kinoshita M, Tanaka M
Dept. of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hepatogastroenterology. 1999 Jul-Aug;46(28):2575-81.
BACKGROUND/AIMS: The Ki-ras gene located at 12p, encodes the GTP binding protein involving the signal transduction system and concerns cell proliferation and differentiation.
Pancreatic tissues were obtained from 37 patients with various pancreatic diseases. Ki-ras codon 12 point mutation and p53 (exon 5-8) mutation were examined in 3 patients with chronic pancreatitis, 9 mucinous adenoma of the pancreas (2 with mucinous cystadenoma and 7 with intraductal papillary-mucinous adenoma), 22 pancreatic ductal carcinoma, and 3 serous cystadenoma.
On usual pancreatic exocrine ductal lesions, Ki-ras point mutation was evident in 0% (0/3) of chronic pancreatitis, in 56% (5/9) of mucinous adenoma, and in 57% (12/21) of ductal carcinoma, the mutation being located in the second letter in 18 and in the 1st letter in 2. One Ki-ras codon 12 positive pancreatic cancer showed Ki-ras codon 12 point mutation in the surrounding pancreas (2nd letter mutation in both areas). p53 mutation was present in 0% (0/1) of chronic pancreatitis, in 0% (0/8) of mucinous adenoma, while it was evident in 29% (6/21) of pancreatic ductal carcinoma, the mutation being situated in exon 5 in 3, in exon 6 in 1, and in exon 7 in 2. In 3 patients with serous cystadenoma, there was no mutation in Ki-ras codon 12 or p53 (exon 5-8).
These findings suggest that Ki-ras point mutation is involved in the early events of pancreatic ductal carcinoma, while p53 mutation is intricated in the late phase of pancreatic ductal carcinogenesis and the histogenesis of serous cystadenoma is different from that of pancreatic exocrine ductal lesions including mucinous adenoma and ductal carcinoma.
背景/目的：位于12p的Ki-ras基因编码参与信号转导系统的GTP结合蛋白，与细胞增殖和分化有关。
从37例患有各种胰腺疾病的患者中获取胰腺组织。检测了3例慢性胰腺炎、9例胰腺黏液性腺瘤（2例黏液性囊腺瘤和7例导管内乳头状黏液性腺瘤）、22例胰腺导管癌和3例浆液性囊腺瘤患者的Ki-ras密码子12点突变和p53（外显子5-8）突变。
在常见的胰腺外分泌导管病变中，慢性胰腺炎的Ki-ras点突变率为0%（0/3），黏液性腺瘤为56%（5/9），导管癌为57%（12/21），其中18例突变位于第二位碱基，2例位于第一位碱基。1例Ki-ras密码子12阳性的胰腺癌在周围胰腺中也显示Ki-ras密码子12点突变（两个区域均为第二位碱基突变）。慢性胰腺炎的p53突变率为0%（0/1），黏液性腺瘤为0%（0/8），而胰腺导管癌为29%（6/21），其中3例突变位于外显子5，1例位于外显子6，2例位于外显子7。3例浆液性囊腺瘤患者的Ki-ras密码子12或p53（外显子5-8）均无突变。
这些发现表明，Ki-ras点突变参与胰腺导管癌的早期事件，而p53突变与胰腺导管癌发生的晚期有关，浆液性囊腺瘤的组织发生与包括黏液性腺瘤和导管癌在内的胰腺外分泌导管病变不同。
