Involvement of mutations in the DPC4 promoter in endometrial carcinoma development.

Involvement of mutations in the DPC4 promoter in endometrial carcinoma development.
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DPC4 启动子突变参与子宫内膜癌的发生。

DOI:
10.1002/(sici)1098-2744(199905)25:1
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发表时间:
1999
影响因子:
4.6
通讯作者:
Wake,N
Wake,N
中科院分区:
医学2区
文献类型:
--
作者:
Zhou,Y;Kato,H;Shan,D;Minami,R;Kitazawa,S;Matsuda,T;Arima,T;Barrett,JC;Wake,N

文献摘要

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To define the target of chromosome 18q loss of heterozygosity, which is prevalent in endometrial carcinomas, we made a deletion map from 64 tumors. Loss of heterozygosity on 18q was found in 20 tumors. Among these, 14 tumors carried deletions at the 18q21.1 region, where theDPC4gene is located.DPC4transcription was disturbed in all six of the tumors with deletions at 18q21.1 examined, which sharply contrasted with the positive transcription in 12 tumors that retained heterozygosity at the 18q21.1 region. However, in the 14 tumors with the 18q21.1 deletions, the remaining allele had the wild‐type sequence of theDPC4coding region instead of somatic mutations in theDPC4coding region. We found a one‐ and two‐base substitutions in theDPC4promoter in two of the six tumors that showed disturbedDPC4transcription. Chloramphenicol acetyltransferase assays clearly demonstrated that the mutant promoters had the potential to suppress or silenceDPC4transcription, implicating theDPC4gene in endometrial carcinoma.Mol. Carcinog. 25:64–72, 1999.© 1999 Wiley‐Liss, Inc.