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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
K-ras gene point mutations and p21ras immunostaining in human ovarian tumors
A Semczuk1, K Postawski, D Przadka
12nd Department of Gynecology, University School of Medicine, Lublin, Poland.
Abstract:
It is well recognized that genetic alterations within oncogenes, tumor suppressor genes, DNA mismatch repair and excision repair genes contribute to tumorigenesis within the human ovary. This study was undertaken to screen for the existence of K-ras gene point mutations in paraffin-embedded slides randomly selected from benign and malignant ovarian tumors applying the PCR-RFLP technique. Expression of p21ras was also assessed in 30 primary ovarian adenocarcinomas immunohistochemically. K-ras codon 12 point mutations occurred in nine of 40 (22.5%) cases. They were not identified in two benign mucinous cystadenomas, but in one out of two (50%) mucinous tumors of LMP (low malignant potential), in five out of 30 (17%) ovarian adenocarcinomas, and in one case of adenocarcinoma metastatic to the ovary. K-ras activation was also detected in one out of four (25%) sex cord-stromal cell tumors (folliculoma), and in one dysgerminoma. None of these tumors exhibited K-ras codon 13 point mutations. Gene alterations were more frequently found in mucinous than in non-mucinous (30% vs 10%) tumors, although the difference did not reach significance (p > 0.05). The frequency of K-ras point mutations was correlated neither with clinical nor with pathological variables of cancer. Cytoplasmic p21ras was expressed in all adenocarcinomas negative for K-ras point mutations, whereas one of five (20%) K-ras-positive tumors exhibited lack of immunoreactivity. In conclusion, these findings confirm the role of K-ras activation in mucinous ovarian tumors. p21ras expression is not necessarily associated with K-ras gene alterations in human ovarian adenocarcinomas.
Insights
K-ras gene mutations were found in 22.5% of ovarian tumors, particularly in mucinous types. p21ras protein expression was not always linked to these K-ras gene alterations in ovarian adenocarcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Genetic alterations in oncogenes and DNA repair genes are implicated in ovarian tumorigenesis.
- K-ras gene mutations are known contributors to various cancers.
Purpose of the Study:
- To investigate the presence of K-ras gene point mutations in benign and malignant ovarian tumors.
- To assess the expression of p21ras protein in ovarian adenocarcinomas.
Main Methods:
- PCR-RFLP technique was used to screen for K-ras gene point mutations in paraffin-embedded ovarian tumor samples.
- Immunohistochemistry was employed to evaluate p21ras protein expression in 30 primary ovarian adenocarcinomas.
Main Results:
- K-ras codon 12 point mutations were identified in 22.5% of the 40 ovarian tumors analyzed.
- Mutations were detected in mucinous tumors of low malignant potential, adenocarcinomas, metastatic adenocarcinoma, sex cord-stromal tumors, and a dysgerminoma.
- p21ras was expressed in all K-ras-negative adenocarcinomas, but lacking in 20% of K-ras-positive tumors.
Conclusions:
- K-ras gene activation plays a role in the development of mucinous ovarian tumors.
- p21ras expression in ovarian adenocarcinomas is not consistently associated with K-ras gene alterations.
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