Integrated mutation analysis in colorectal cancer

结直肠癌的综合突变分析

基本信息

批准号：
08407037
负责人：
KITAYAMA Joji
金额：
$ 24.06万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1999
项目状态：
已结题

项目摘要

Recent studies have shown that many genetic changes such as apc, ras, p53 and microsattelite instability, were involved in the development of colorectal cancers. We analyzed those genetic mutations in many clinical samples resected in our institute, and examined the mechanisms of colorectal cancer, and apotosis mechanisms and radiochemosensitivity.1. In "so called" non-polypoid cancer ; DNA from 63 adenomas (31 polypoid, 17 superficial elevated, 15 superficial depressed), 66 sm carcinomas (47 polypoid, 19non-polypoid) and 34 advance carcinomas were examined for K-ras codon 12 point mutations and APC mutations in the mutation cluster region. K-ras mutation : The frequency in superficial depressed adenomas was lower than that in polypoid adenomas (0% vs. 31% : p=0.018). The frequency in non-polypoid carcinomas was lower than that in polypoid carcinomas (11% vs. 56% : p=0.0008), and was relatively low compared with that in polypoid adenomas (11% vs. 31%). The frequency in superficial depressed adenomas was lower than that in polypoid adenomas (7% vs. 43% : p=0.016), and that in polypoid carcinomas was similar to that in non-polypoid carcinomas. In this non-polypoid pathway, APC mutation seems to be requisite, but K-ras mutation not. It is possible that new APC mutations are acquired after the development of superficial depressed adenomas.2. Transfection of antisense of Bcl-XL, but not of Bcl-2, significantly increased the sensitivity to 5-Fu in colorectal cancer cells. This indicates suppression of apotosis through Bcl-XL is critically involved in the effects of 5-Fu.3. P53 and p21 were examined in surgical specimens of rectal cancers immunohistocchemically. The expression of p21, but not of p53, was sell correlated with the sensitivity of preoperative irradiation. This supports the effectiveness of the radiation therapy with p21 positive advanced rectal cancers.

最近的研究表明，许多遗传变化，例如APC，RAS，p53和微观不稳定性，都参与了结直肠癌的发展。我们分析了我们研究所切除的许多临床样本中的遗传突变，并检查了结直肠癌的机制，以及凋亡机制和放射性化学敏感性。1。在“所谓”非型癌症中；检查了63个腺瘤（31个息肉样子，17个表面抬高，15个表面抑郁症），66个SM癌（47个息肉样子，19NON-多型体）和34个先进的癌中的K-RAS密码子12点突变和APC突变中的K-RAS CORDASS突变突变。。 K-RAS突变：表面抑郁症腺瘤的频率低于息肉腺瘤（0％vs. 31％：P = 0.018）的频率。非多型癌的频率低于多型癌（11％比56％：p = 0.0008）的频率，与多型腺瘤腺瘤（11％vs. 31％）相比相对较低。表面抑郁症的腺瘤的频率低于多型腺瘤（7％vs. 43％：P = 0.016），而多型癌中的频率与非多型癌中的频率相似。在这种非型途径中，APC突变似乎是必需的，但K-Ras突变不是。在浅表抑郁症腺瘤的发展后，可能会获得新的APC突变。 Bcl-XL的反义但不是Bcl-2的转染，显着提高了结直肠癌细胞中对5-FU的敏感性。这表明通过BCL-XL抑制凋亡与5-FU.3的影响至关重要。在直肠癌免疫组织化学的外科手术标本中检查了p53和p21。 p21的表达（而不是p53的表达）与术前照射的敏感性相关。这支持P21阳性直肠癌的辐射疗法的有效性。