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Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary
To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K‐ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinom...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
1994
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919385/ https://www.ncbi.nlm.nih.gov/pubmed/7852189 http://dx.doi.org/10.1111/j.1349-7006.1994.tb02937.x |
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author | Fujita, Masami Enomoto, Takayuki Inoue, Masaki Tanizawa, Osamu Ozaki, Masami Rice, Jerry M. Nomura, Taisei |
author_facet | Fujita, Masami Enomoto, Takayuki Inoue, Masaki Tanizawa, Osamu Ozaki, Masami Rice, Jerry M. Nomura, Taisei |
author_sort | Fujita, Masami |
collection | PubMed |
description | To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K‐ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mutinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single‐strand conformation polymorphism (SSCP) analysis of polymerase chain reaction(PCR)‐amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by SSCP analysis of PCR‐amplifled fragments. Mutations were found in 22 of 70 (31%) ovarian tumors, including 1 of 5 mucinous tumors of borderline malignancy. Mutations were subsequently characterized by direct sequencing. Single missense base substitutions were detected in 13 ovarian carcinomas and in one case of mucinous tumor of borderline malignancy. Short (1‐8 bp) deletions and insertions were found in 8 cases. Mutations in the p53 gene occurred more frequently in serous adenocarcinomas (14/31, 45%) than in all nonserous types of malignant epithelial tumors combined (7/34, 21%;P=0.032). Point mutations in K‐ras were identified by dot blot hybridization analysis of PCR‐amplified fragments with mutation‐specific oligonucleotides and by direct sequencing. The overall frequency of K‐ras mutations was 19/70 (27%).K‐ras mutations were found in 12 of 17 (71%) mucinous tumors (8/12 mucinous carcinomas [67%] and 4/5 mucinous tumors of borderline malignancy [80%]), and occurred more frequently than in serous carcinomas (4/31, 13%;P=0.00009) or in all nonmucinous types of ovarian epithelial tumors combined (7/53, 13%; p=0.00002). These data suggest that different combinations of oncogenes and/or tumor suppressor genes may be involved in the genesis and development of histologically distinct categories of common epithelial tumors of the human ovary. |
format | Online Article Text |
id | pubmed-5919385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1994 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59193852018-05-11 Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary Fujita, Masami Enomoto, Takayuki Inoue, Masaki Tanizawa, Osamu Ozaki, Masami Rice, Jerry M. Nomura, Taisei Jpn J Cancer Res Article To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K‐ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mutinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single‐strand conformation polymorphism (SSCP) analysis of polymerase chain reaction(PCR)‐amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by SSCP analysis of PCR‐amplifled fragments. Mutations were found in 22 of 70 (31%) ovarian tumors, including 1 of 5 mucinous tumors of borderline malignancy. Mutations were subsequently characterized by direct sequencing. Single missense base substitutions were detected in 13 ovarian carcinomas and in one case of mucinous tumor of borderline malignancy. Short (1‐8 bp) deletions and insertions were found in 8 cases. Mutations in the p53 gene occurred more frequently in serous adenocarcinomas (14/31, 45%) than in all nonserous types of malignant epithelial tumors combined (7/34, 21%;P=0.032). Point mutations in K‐ras were identified by dot blot hybridization analysis of PCR‐amplified fragments with mutation‐specific oligonucleotides and by direct sequencing. The overall frequency of K‐ras mutations was 19/70 (27%).K‐ras mutations were found in 12 of 17 (71%) mucinous tumors (8/12 mucinous carcinomas [67%] and 4/5 mucinous tumors of borderline malignancy [80%]), and occurred more frequently than in serous carcinomas (4/31, 13%;P=0.00009) or in all nonmucinous types of ovarian epithelial tumors combined (7/53, 13%; p=0.00002). These data suggest that different combinations of oncogenes and/or tumor suppressor genes may be involved in the genesis and development of histologically distinct categories of common epithelial tumors of the human ovary. Blackwell Publishing Ltd 1994-12 /pmc/articles/PMC5919385/ /pubmed/7852189 http://dx.doi.org/10.1111/j.1349-7006.1994.tb02937.x Text en |
spellingShingle | Article Fujita, Masami Enomoto, Takayuki Inoue, Masaki Tanizawa, Osamu Ozaki, Masami Rice, Jerry M. Nomura, Taisei Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary |
title | Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary |
title_full | Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary |
title_fullStr | Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary |
title_full_unstemmed | Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary |
title_short | Alteration of the p53 Tumor Suppressor Gene Occurs Independently of K‐ras Activation and More Frequently in Serous Adenocarcinomas than in Other Common Epithelial Tumors of the Human Ovary |
title_sort | alteration of the p53 tumor suppressor gene occurs independently of k‐ras activation and more frequently in serous adenocarcinomas than in other common epithelial tumors of the human ovary |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919385/ https://www.ncbi.nlm.nih.gov/pubmed/7852189 http://dx.doi.org/10.1111/j.1349-7006.1994.tb02937.x |
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