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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...

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Autores principales: Fujita, Masami, Enomoto, Takayuki, Inoue, Masaki, Tanizawa, Osamu, Ozaki, Masami, Rice, Jerry M., Nomura, Taisei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1994
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.
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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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