Frequent p53 mutation in brain (fetal)-type glycogen phosphorylase positive foci adjacent to human 'de novo' colorectal carcinomas.
Frequent p53 mutation in brain (fetal)-type glycogen phosphorylase positive foci adjacent to human 'de novo' colorectal carcinomas.
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DOI：
10.1054/bjoc.2001.1824
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发表时间：
2001-06-01
影响因子：
8.8
通讯作者：
Ogawa M
中科院分区：
文献类型：
--
作者：
Shimada S;Shiomori K;Tashima S;Tsuruta J;Ogawa M
除了“腺瘤癌序列”外，“从头”癌变被认为是导致结直肠癌的另一个主要途径。我们最近的研究表明，脑（胎儿）型糖原磷酸化酶（BGP）阳性灶（BGP灶）的分布与“原发”癌的发生部位有密切关系。本研究的目的是调查BGP病灶的遗传改变，并描述它们在“从头”癌变过程中的特征。从96例结直肠癌标本中筛选出17例同时表达p53和BGP蛋白的大肠癌。应用聚合酶链反应-单链构象多态性（PCR-SSCP）技术检测BGP病灶、BGP阴性粘膜及癌组织中增殖细胞核抗原（PCNA）标记指数、p53和K-ras基因第12密码子突变。所有病例的癌旁移行粘膜中均可见散在的BGP灶。BGP病灶的PCNA标记指数明显高于BGP阴性粘膜（P< 0.001）。p53基因突变8例，K-ras基因突变均未检出。有趣的是，虽然在BGP阳性灶中没有检测到p53蛋白的过度表达，但尽管没有K-ras突变，但p53基因频繁突变（占所检测的BGP灶的41.2%）。目前的研究表明，潜在的癌前病变在结直肠移行粘膜与频繁的p53基因突变。这表明，BGP病灶是有前途的候选人，为进一步调查的'从头'结直肠癌发生。© 2001癌症研究运动http://www.bjcancer.com
‘de novo’ carcinogenesis has been advocated besides ‘adenoma carcinoma sequence’ as another dominant pathway leading to colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of ‘de novo’ carcinoma. The aims of the present study are to investigate genetic alteration in the BGP foci and to characterize them in the ‘de novo’ carcinogenesis. 17 colorectal carcinomas without any adenoma component expressing both immunoreactive p53 and BGP protein were selected from 96 resected specimens from our previous study. Further investigations to examine the proliferating cell nuclear antigen (PCNA)-labelling index, and the p53 and the codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the carcinoma in all cases. The PCNA labelling index in the BGP foci was significantly higher than that in the BGP negative mucosa (P< 0.001). p53 mutations were observed in 8 carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53 protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2% of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of ‘de novo’ colorectal carcinogenesis. © 2001Cancer Research Campaign http://www.bjcancer.com
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DOI：
10.1016/0006-3002(56)90273-6
发表时间：
1956-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
KREBS, EG;FISCHER, EH
通讯作者：
FISCHER, EH
DOI：
10.1097/00008469-199210000-00006
发表时间：
1992-10-01
期刊：
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
影响因子：
--
作者：
Brito, M J;Filipe, M I;Morris, R W
通讯作者：
Morris, R W
DOI：
10.1016/0169-328x(89)90052-1
发表时间：
1989-11-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
GELINAS, RP;FROMAN, BE;GORIN, FA
通讯作者：
GORIN, FA
影响因子：
3.5
作者：
Matsuzaki, H;Shimada, S;Ogawa, M
通讯作者：
Ogawa, M
DOI：
10.1007/s004280050114
发表时间：
1997-12-01
期刊：
VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY
影响因子：
--
作者：
Lisboa, BW;Vogtländer, S;Löning, T
通讯作者：
Löning, T