TY - JOUR
T1 - Analyses of p53 gene mutations in primary human bladder cancer
AU - Miyamoto, Hiroshi
AU - Kubota, Yoshinobu
AU - Shuin, Taro
AU - Torigoe, Soichiro
AU - Hosaka, Masahiko
AU - Iwasaki, Yoshiko
AU - Danenberg, Kathleen
AU - Danenberg, Peter V.
PY - 1993
Y1 - 1993
N2 - Mutations in the tumor suppressor gene p53 have been detected in many tumors. p53 gene mutations are also known to be involved in the progression of human bladder cancers. We investigated structural alterations in the entire coding region of the p53 gene in primary human bladder cancers, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. Of 25 samples obtained from patients, 6 (24%) were found to have p53 alterations. DNA sequencing of the PCR products revealed 6 point mutations resulting in single amino-acid substitutions in the regions of exons 5, 6, 7, 8, and 10 of this gene, respectively. Five of 6 cases with p53 mutations were invasive, with metastasis or high-grade tumors. Interestingly, the one remaining case was a recurrent, low-grade, and superficial (pTa) tumor. In this early stage tumor, allelic loss of the p53 gene was also found, using a polymerase chain reaction-based restriction fragment length polymorphism assay. Our findings are in agreement with previous observations that p53 mutations occurred in a high percentage of high grade or invasive bladder cancers. Since mutation and allelic oss of the p53 gene were also detected in a low-grade and low-stage tumor in the present study, it is suggested that the p53 gene is involved in early stages of some bladder cancers as well as in their late stages.
AB - Mutations in the tumor suppressor gene p53 have been detected in many tumors. p53 gene mutations are also known to be involved in the progression of human bladder cancers. We investigated structural alterations in the entire coding region of the p53 gene in primary human bladder cancers, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. Of 25 samples obtained from patients, 6 (24%) were found to have p53 alterations. DNA sequencing of the PCR products revealed 6 point mutations resulting in single amino-acid substitutions in the regions of exons 5, 6, 7, 8, and 10 of this gene, respectively. Five of 6 cases with p53 mutations were invasive, with metastasis or high-grade tumors. Interestingly, the one remaining case was a recurrent, low-grade, and superficial (pTa) tumor. In this early stage tumor, allelic loss of the p53 gene was also found, using a polymerase chain reaction-based restriction fragment length polymorphism assay. Our findings are in agreement with previous observations that p53 mutations occurred in a high percentage of high grade or invasive bladder cancers. Since mutation and allelic oss of the p53 gene were also detected in a low-grade and low-stage tumor in the present study, it is suggested that the p53 gene is involved in early stages of some bladder cancers as well as in their late stages.
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M3 - Article
C2 - 8123944
AN - SCOPUS:0027717766
SN - 0965-0407
VL - 5
SP - 245
EP - 249
JO - Oncology Research
JF - Oncology Research
IS - 6-7
ER -