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K-ras activation in neoplasms of the human female reproductive tract
T Enomoto1, M Inoue, A O Perantoni
1Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201.
Abstract:
The role of cellular oncogenes in the development of epithelial tumors of the human female reproductive tract has not previously been extensively studied. DNAs isolated from ten human uterine, 13 ovarian, and four cervical neoplasms and from three cell lines derived from endometrial adenocarcinoma were investigated by dot blot hybridization after polymerase chain reaction amplification of ras gene sequences and in some cases by NIH 3T3 transfection. Transforming activity was found in two of nine endometrial adenocarcinomas, but none of seven ovarian carcinomas and none of four cervical carcinomas showed transforming activity. K-ras sequences with a GGT----GAT mutation in codon 12 were demonstrated in both transformants derived from endometrial carcinoma. K-ras codon 12 mutations were similarly detected in six of 13 endometrial carcinomas (one GAT and GCT, one GTT and GCT, two GAT, two GTT) and two of 13 ovarian tumors (GAT and GCT, GAT), both mucinous adenocarcinomas. Point mutation of K-ras in codon 12 is thus comparably frequent in uterine endometrial carcinomas and in colorectal carcinomas and may have similar significance as an event that contributes to progression of these tumors. Cervical carcinomas and ovarian tumors in general, with the possible exception of mucinous adenocarcinoma of the ovary, do not appear to have this characteristic.
Insights
This study investigated ras gene mutations in female reproductive tract cancers. K-ras codon 12 mutations were frequent in endometrial and some ovarian cancers, suggesting a role in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cellular oncogenes, particularly ras genes, are implicated in various cancers.
- The role of ras gene mutations in human female reproductive tract epithelial tumors remains underexplored.
Purpose of the Study:
- To investigate the presence and significance of ras gene mutations in uterine, ovarian, and cervical neoplasms.
- To determine if ras gene mutations contribute to the development and progression of these tumors.
Main Methods:
- DNA isolation from human tumor samples and cell lines.
- Polymerase chain reaction (PCR) amplification of ras gene sequences.
- Dot blot hybridization and NIH 3T3 transfection assays to detect transforming activity and specific mutations.
Main Results:
- Transforming activity was detected in two of nine endometrial adenocarcinomas.
- K-ras codon 12 mutations (GGT to GAT) were identified in these transformants.
- K-ras codon 12 mutations were found in 6/13 endometrial carcinomas and 2/13 ovarian mucinous adenocarcinomas.
- No transforming activity or K-ras mutations were observed in cervical carcinomas and most ovarian carcinomas.
Conclusions:
- Point mutations in K-ras codon 12 are frequent in endometrial carcinomas, similar to colorectal carcinomas, and may drive tumor progression.
- Cervical carcinomas and most ovarian tumors do not appear to harbor these specific K-ras mutations.
- Mucinous adenocarcinoma of the ovary may represent an exception regarding K-ras codon 12 mutations.