Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis - Proposal for new molecular profile of colorectal carcinomas
Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis - Proposal for new molecular profile of colorectal carcinomas
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DOI：
10.2353/jmoldx.2006.050052
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发表时间：
2006-05-01
影响因子：
4.1
通讯作者：
Nakamura, S
中科院分区：
文献类型：
--
作者：
Sugai, T;Habano, W;Nakamura, S
以阐明结直肠癌的不同基因图谱。根据肿瘤的部位(左侧和右侧)，我们评估了119例结直肠癌组织中杂合性缺失(LOH)、CpG岛甲基化表型(CIMP)、微卫星不稳定性(MSI)以及P53、Ki-ras和APC基因的突变情况。分别用微卫星聚合酶链式反应和甲基化特异性聚合酶链式反应结合隐窝分离方法检测LOH(5q、8p、17p、18q和22q)、MSI和CIMP(MINT1、MIN72、MINT31、MLH-1、MGMT、p14、p16和RASSF1A)的状态。此外，还检测了P53、Ki-ras和APC基因的突变。LOH、MSI和CIMP状态使我们可以将样本分为两组：低或阴性和高或阳性。左侧癌组织中P53基因突变率显著高于右侧癌组织，右侧癌组织中CIMP-High和MSI阳性突变频率明显高于左侧癌组织。最后，在结直肠癌中发现了位置特定的甲基化位点：I型(在右侧癌中占优势)和II型(在两种癌症中都常见)。我们的数据证实，结直肠癌的不同分子通路在左侧和右侧肠道中占主导地位。
To clarify distinct genetic profiles of colorectal. cancers based on tumor location (left and right sided), we evalu ated the status of loss of heterozygosity (LOH), CpG islands methylation phenotype (CIMP), microsatellite instability (MSI), and mutations of p53, Ki-ras, and APC genes in 119 colorectal cancers. Statuses of LOH (at 5q, 8p, 17p, 18q, and 22q), MSI, and CIMP (MINT1, MIN72, MINT31, MLH-1,MGMT, p14, p16, and RASSF1A) were determined using microsatellite polymerase chain reaction and methylation-specific polymerase chain reaction coupled with a crypt isolation method, respectively. In addition, mutations of p53, Ki-ras, and APC genes were also examined. LOH, MSI, and CIMP status allowed us to classify samples into two groups: low or negative and high or positive. Whereas the frequency of p53 mutations in the LOH-high status was significantly higher in left-sided cancers than in right sided cancers, CIMP-high in the LOH-high status and MSI-positive status were more frequently found in right sided cancers compared with left sided cancers. Finally, location-specific methylated loci were seen in colorectal cancers: type I (dominant in right-sided cancer) and type II (common in both segments of cancer). Our data confirm that distinct molecular pathways to colorectal cancer dominate in the left and right sides of the bowel.