Genetic pathways of 'de novo' colorectal carcinomas with reference to fetal-type glycogen phosphorylase positive foci.
Genetic pathways of 'de novo' colorectal carcinomas with reference to fetal-type glycogen phosphorylase positive foci.
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DOI：
10.3892/ijo.22.1.65
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发表时间：
2003
影响因子：
5.2
通讯作者：
K. Shiomori;S. Shimada;Takashi Marutsuka;I. Hatayama;M. Ogawa
中科院分区：
文献类型：
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作者：
K. Shiomori;S. Shimada;Takashi Marutsuka;I. Hatayama;M. Ogawa
“从头”癌变被认为是继“腺瘤癌变序列”之后导致结直肠癌的另一条主要途径。我们的前期研究表明，移行粘膜中脑（胎儿）型糖原磷酸化酶（BGP）阳性灶（BGP灶）存在频繁的p53突变，BGP灶的分布与“原发”癌的发生部位密切相关。本研究的目的是进一步研究BGP病灶的遗传改变，并阐明“从头”致癌的机制。从168例手术切除的结直肠癌标本中，选择28例浸润到粘膜下层或固有肌层浅而无任何腺瘤成分表达免疫反应性p53蛋白的结直肠癌。应用PCR-SSCP和DNA测序技术对BGP病灶、BGP阴性大肠粘膜和原发癌中p53、K-ras和APC基因突变进行了研究。28例癌组织中BGP免疫反应均为阳性，癌旁粘膜中可见散在的BGP灶。所有病例的癌灶和BGP灶均未发现K-ras基因突变。p53和APC突变在原发癌中分别为14例（50.0%）和9例（32.1%），在BGP灶中分别为11例（39.3%）和1例（3.6%）。在28例癌和BGP阳性灶中，p53和APC同时突变分别为8例和1例，p53单独突变分别为6例和10例，APC单独突变分别为1例和0例。这些结果表明，BGP灶可能在p53基因频繁改变的“从头”结直肠癌发生中起着非常重要的作用，并且可能存在两个主要途径，即，p53-APC通路和p53单独通路，来自BGP病灶和“新生”癌之间的遗传改变链。
'De novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to the colorectal carcinoma. Our previous study demonstrated that brain (fetal)-type glycogen phosphorylase (BGP) positive foci in the transitional mucosa (BGP foci) have frequent p53 mutations and that the distribution of BGP foci has a close relationship with the location of 'de novo' carcinoma. The aims of the present study were to investigate further genetic alterations in the BGP foci and to clarify the mechanism of 'de novo' carcinogenesis. Twenty-eight colorectal carcinomas with invasion into submucosa or superficial muscularis propria without any adenoma component expressing immunoreactive p53 protein were selected from 168 resected specimens. Investigations of the p53, K-ras and APC mutations was performed in the BGP foci, BGP negative colorectal mucosa and 'de novo' carcinoma using PCR-SSCP and DNA squencing. In all 28 cases, immunoreactive BGP was positive in the carcinomas and the BGP foci were observed sporadically in the mucosa adjacent to the carcinoma. No K-ras mutation was observed in either carcinoma or BGP foci in any of the cases. Mutations of p53 and APC were 14 (50.0%) and 9 (32.1%) in 'de novo' carcinomas, and 11 (39.3%) and 1 (3.6%) in BGP foci, respectively. Both p53 and APC mutations were detected in 8 and 1, p53 mutation alone in 6 and 10, APC mutation alone in 1 and 0 out of 28 carcinomas and BGP positive foci, respectively. These results suggest that the BGP foci may play a very important role in the 'de novo' colorectal carcinogenesis from the frequent genetic alterations of p53, and that there may be two major pathways, i.e., the p53-APC pathway and the p53 alone pathway, from the chain of genetic alterations between BGP foci and 'de novo' carcinoma.