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本文引用的文献

1
Promoter hypermethylation leads to decreased APC mRNA expression in familial polyposis and sporadic colorectal tumours, but does not substitute for truncating mutations.启动子高甲基化导致家族性腺瘤性息肉病和散发性结直肠癌中APC信使核糖核酸表达降低,但不能替代截短突变。
Exp Mol Pathol. 2008 Dec;85(3):201-6. doi: 10.1016/j.yexmp.2008.09.006. Epub 2008 Oct 11.
2
APC and the three-hit hypothesis.APC与三击假说
Oncogene. 2009 Jan 8;28(1):146-55. doi: 10.1038/onc.2008.361. Epub 2008 Oct 6.
3
Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers.基因表达谱分析显示,髓样乳腺癌是基底样乳腺癌的一个亚组。
Cancer Res. 2006 May 1;66(9):4636-44. doi: 10.1158/0008-5472.CAN-06-0031.
4
Linear models and empirical bayes methods for assessing differential expression in microarray experiments.用于评估微阵列实验中差异表达的线性模型和经验贝叶斯方法。
Stat Appl Genet Mol Biol. 2004;3:Article3. doi: 10.2202/1544-6115.1027. Epub 2004 Feb 12.
5
Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation.轻度家族性腺瘤性息肉病的疾病严重程度和遗传途径差异很大,但取决于种系突变的位点。
Gut. 2006 Oct;55(10):1440-8. doi: 10.1136/gut.2005.087106. Epub 2006 Feb 4.
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Retention of chromosome arm 5q in stage II colon cancers identifies 83% of liver metastasis occurrences.
Genes Chromosomes Cancer. 2006 Jan;45(1):94-102. doi: 10.1002/gcc.20269.
7
Refining the relation between 'first hits' and 'second hits' at the APC locus: the 'loose fit' model and evidence for differences in somatic mutation spectra among patients.优化APC基因座处“首次打击”与“二次打击”之间的关系:“宽松拟合”模型及患者间体细胞突变谱差异的证据。
Oncogene. 2003 Jul 3;22(27):4257-65. doi: 10.1038/sj.onc.1206471.
8
Analysis of chromosomal instability in human colorectal adenomas with two mutational hits at APC.对具有两个APC突变位点的人结肠直肠腺瘤中染色体不稳定性的分析。
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16910-5. doi: 10.1073/pnas.012679099. Epub 2002 Dec 16.
9
The 'just-right' signaling model: APC somatic mutations are selected based on a specific level of activation of the beta-catenin signaling cascade.“恰到好处”的信号传导模型:APC体细胞突变是根据β-连环蛋白信号级联的特定激活水平来选择的。
Hum Mol Genet. 2002 Jun 15;11(13):1549-60. doi: 10.1093/hmg/11.13.1549.
10
Different combinations of biallelic APC mutation confer different growth advantages in colorectal tumours.
Cancer Res. 2002 Jan 15;62(2):363-6.

根据 APC 基因状态的 II 期结肠癌的表达谱。

Expression Profiles in Stage II Colon Cancer According to APC Gene Status.

机构信息

Centre de Recherche en Cancérologie de Marseille, INSERM, UMR891, Marseille, France.

出版信息

Transl Oncol. 2012 Apr;5(2):72-6. doi: 10.1593/tlo.11325. Epub 2012 Apr 1.

DOI:10.1593/tlo.11325
PMID:22496922
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3323927/
Abstract

Colorectal cancer is one of the most common cancers in the world. Histoclinical staging is efficient, but combination with molecular markers may improve the classification of stage II cancers. Several tumor-suppressor genes have been associated with colorectal cancer, and the most frequent allelic losses have been extensively studied for their prognosis effect, but the results remain controversial. In a previous study, we found a possible influence of the chromosome 5 status in the development of liver metastases in stage II colon cancers. We have here investigated the role of the APC gene, located in chromosome arm 5q, in a series of 183 colon adenocarcinomas through a combined analysis of gene expression, mutation, allelic loss and promoter methylation, and metastasis occurrence. Point mutations were found in 73% of cases and allelic losses were found in 39%; 59% of tumors presented with a biallelic inactivation, with a very strong interdependence of the two APC hits (P = 2.1 x 10(-9)). No association was found between expression, number and type of APC alterations, and metastatic evolution. Our results show that the determination of APC status cannot help in the prediction of metastasis and cannot be used to subclassify stage II colon cancers.

摘要

结直肠癌是世界上最常见的癌症之一。组织临床分期是有效的,但与分子标志物相结合可能会改善 II 期癌症的分类。已经有几个肿瘤抑制基因与结直肠癌相关联,并且已经对最常见的等位基因缺失进行了广泛研究,以评估其预后效果,但结果仍存在争议。在之前的一项研究中,我们发现染色体 5 状态可能会影响 II 期结肠癌肝转移的发生。我们通过联合分析基因表达、突变、等位基因缺失和启动子甲基化以及转移发生情况,研究了位于染色体 5q 臂上的 APC 基因在 183 例结肠腺癌中的作用。我们发现 73%的病例存在点突变,39%的病例存在等位基因缺失;59%的肿瘤表现为双等位基因失活,两个 APC 靶点的相互依赖性非常强(P = 2.1 x 10(-9))。APC 改变的表达、数量和类型与转移进化之间没有关联。我们的结果表明,APC 状态的确定不能帮助预测转移,也不能用于对 II 期结肠癌进行亚分类。