The APC/β-catenin pathway in ulcerative colitis-related colorectal carcinomas -: A mutational analysis
The APC/β-catenin pathway in ulcerative colitis-related colorectal carcinomas -: A mutational analysis
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DOI：
10.1002/cncr.10334
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发表时间：
2002-03-01
期刊：
影响因子：
6.2
通讯作者：
Waldman, FM
中科院分区：
文献类型：
--
作者：
Aust, DE;Terdiman, JP;Waldman, FM
背景：尽管已知APC/β -连环蛋白通路在散发性结直肠癌发生中起关键作用，但其对溃疡性结肠炎（UC）相关肿瘤进展的影响尚不清楚。为阐明APC/β -连环蛋白通路在UC相关癌症发生中的作用，作者在一组UC相关和散发性结直肠癌中鉴定了APC和β -连环蛋白突变。
方法：对APC的突变聚集区（密码子1267至1529）和β -连环蛋白的外显子3进行直接测序。
结果：30例UC相关肿瘤中仅有1例（3%）显示APC突变，而42例散发性癌中有11例（26%）在突变聚集区内有突变。在散发性癌组中，右侧癌仅有87例显示APC突变，而左侧癌50%在突变聚集区内有突变。两组中的肿瘤均未显示β -连环蛋白突变。
结论：APC和β -连环蛋白突变在UC相关肿瘤中罕见。这些基因可能因研究区域外的突变或表观遗传沉默而改变。或者，APC/β -连环蛋白信号级联中涉及的其他蛋白质可能改变，或者该通路可能很少参与UC相关癌症发生。右侧和左侧散发性肿瘤之间APC突变频率的显著差异表明这两个肿瘤部位存在不同的分子通路。（C）2002年美国癌症协会
BACKGROUND. Although the APC/beta-catenin pathway is known to play a crucial role in sporadic colorectal carcinogenesis, its influence on ulcerative colitis (UC)-related neoplastic progression is unknown. To elucidate the role of the APC-/beta-catenin pathway in UC-related carcinogenesis, the authors identified APC and beta-catenin mutations in a set of UC-related and sporadic colorectal carcinomas.METHODS. The mutational cluster region of APC (codon 1267 to 1529) and exon 3 of the beta-catenin were directly sequenced.RESULTS. only 1 of 30 UC-related tumors (3%) showed an APC mutation whereas 11 of the 42 sporadic carcinomas (26%) had mutations within the mutational cluster region. Within the sporadic carcinoma group, only 87 of the right-sided carcinomas showed APC mutations whereas 50% of the left-sided carcinomas had mutations within the mutational cluster region. None of the tumors in either group showed a beta-catenin mutation.CONCLUSIONS. Mutations of the APC and beta-catenin are rare in UC-related tumors. These genes may be altered because of mutations outside the regions studied, or by epigenetic silencing. Alternatively, other proteins involved in the APC/beta-catenin signaling cascade may be altered, or this pathway may be involved infrequently in UC-related carcinogenesis. The significant difference in frequency of APC mutations between right- and left-sided sporadic tumors suggests different molecular pathways in these two tumor sites. (C) 2002 American Cancer Society.