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Involvement of mutations in the DPC4 promoter in endometrial carcinoma development
Author(s) -
Zhou Yong,
Kato Hidenori,
Shan Dan,
Minami Rieko,
Kitazawa Sohei,
Matsuda Takao,
Arima Takahiro,
Barrett J. Carl,
Wake Norio
Publication year - 1999
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199905)25:1<64::aid-mc8>3.0.co;2-z
Subject(s) - biology , loss of heterozygosity , genetics , gene , transcription (linguistics) , cancer research , coding region , allele , carcinoma , pseudogene , microbiology and biotechnology , genome , linguistics , philosophy
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 the DPC4 gene is located. DPC4 transcription 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 the DPC4 coding region instead of somatic mutations in the DPC4 coding region. We found a one‐ and two‐base substitutions in the DPC4 promoter in two of the six tumors that showed disturbed DPC4 transcription. Chloramphenicol acetyltransferase assays clearly demonstrated that the mutant promoters had the potential to suppress or silence DPC4 transcription, implicating the DPC4 gene in endometrial carcinoma. Mol. Carcinog. 25:64–72, 1999. © 1999 Wiley‐Liss, Inc.