TY - JOUR
T1 - Involvement of mutations in the DPC4 promoter in endometrial carcinoma development
AU - Zhou, Yong
AU - Kato, Hidenori
AU - Shan, Dan
AU - Minami, Rieko
AU - Kitazawa, Sohei
AU - Matsuda, Takao
AU - Arima, Takahiro
AU - Barrett, J. Carl
AU - Wake, Norio
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - 18q loss of heterozygosity
KW - GATA-2
KW - Loss of DPC4 transcription
KW - c/EBPβ
UR - http://www.scopus.com/inward/record.url?scp=0032936925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032936925&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1098-2744(199905)25:1<64::AID-MC8>3.0.CO;2-Z
DO - 10.1002/(SICI)1098-2744(199905)25:1<64::AID-MC8>3.0.CO;2-Z
M3 - Article
C2 - 10331746
AN - SCOPUS:0032936925
VL - 25
SP - 64
EP - 72
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 1
ER -