Molecular and biological analysis of carcinoma of the small intestine: β-catenin gene mutation by interstitial deletion involving exon 3 and replication error phenotype
Molecular and biological analysis of carcinoma of the small intestine: β-catenin gene mutation by interstitial deletion involving exon 3 and replication error phenotype
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小肠癌的分子和生物学分析：涉及外显子 3 的间质缺失导致 β-catenin 基因突变和复制错误表型
DOI：
10.1111/j.1572-0241.2000.02123.x
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发表时间：
2000
影响因子：
9.8
通讯作者：
T. Shimano
中科院分区：
文献类型：
--
作者：
M. Murata;K. Iwao;Y. Miyoshi;Y. Nagasawa;T. Ohta;Kunitaka Shibata;K. Oda;H. Wada;S. Tominaga;Yasuki Matsuda;M. Ohsawa;Yusuke Nakamura;T. Shimano
小肠癌的遗传机制尚不清楚。我们报告了一例小肠癌的基因改变分析结果。一名59岁妇女在回肠末端切除肿瘤。组织学上，肿瘤为高分化腺癌。我们筛选了大肠腺瘤性息肉病（APC）、β-连环蛋白、K-ras和p53基因以及微卫星不稳定性的遗传改变，这些基因已知与结直肠肿瘤发生有关。肿瘤表现出425 bp的体细胞间质缺失，包括β-catenin基因的整个外显子3。免疫组化染色证实在恶性组织的细胞质和细胞核中有异常的β-连环蛋白积累。此外，在肿瘤DNA中检测到具有复制错误表型的转化生长因子β受体II型基因的移码突变。相比之下，APC、K-ras和p53基因未发现遗传改变。我们的研究结果表明，β-catenin基因突变和复制错误表型都可能参与了本病例小肠肿瘤的癌变。这是首次报道通过体细胞基因突变激活β-catenin基因参与小肠癌的发生发展。
The genetic mechanisms of carcinomas of the small intestine are not well understood. We report the results of analysis of genetic alterations in a case of small intestinal carcinoma. A tumor in the terminal ileum was resected in a 59-yr-old woman. Histologically, the tumor was classified as well-differentiated adenocarcinoma. We screened for genetic alterations in adenomatous polyposis coli (APC), β-catenin, K-ras, and p53 genes, as well as microsatellite instability, which are known to be involved in colorectal tumorigenesis. The tumor exhibited somatic interstitial deletion of 425-bp, which included the entire exon 3 in β-catenin gene. Immunohistochemical staining confirmed accumulation of aberrant β-catenin protein in the cytoplasm and nuclei of the malignant tissue. Furthermore, a frameshift mutation in the transforming growth factor β receptor type II gene with replication error phenotype was detected in the tumor DNA. In contrast, no genetic alterations were found in the APC, K-ras, and p53 genes. Our results suggested that both β-catenin gene mutation and replication error phenotype might contribute to carcinogenesis of the small intestinal tumor in our case. This is the first report that activation of β-catenin gene by somatic gene mutation is involved in the development of carcinoma of the small intestine.
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影响因子：
64.5
作者：
FISHEL, R;LESCOE, MK;KOLODNER, R
通讯作者：
KOLODNER, R
影响因子：
56.9
作者：
PAPADOPOULOS, N;NICOLAIDES, NC;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
56.9
作者：
MARKOWITZ, S;WANG, J;WILLSON, JKV
通讯作者：
WILLSON, JKV
影响因子：
158.5
作者：
VOGELSTEIN, B;FEARON, ER;BOS, JL
通讯作者：
BOS, JL
DOI：
10.1073/pnas.91.21.9871
发表时间：
1994-10-11
影响因子：
11.1
作者：
MAO, L;LEE, DJ;SIDRANSKY, D
通讯作者：
SIDRANSKY, D