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Published on: July 25, 2020
KRAS and MAPK1 gene amplification in type II ovarian carcinomas
Mohammed Tanjimur Rahman1, Kentaro Nakayama, Munmun Rahman
1Departments of Obstetrics and Gynecology, Shimane University School of Medicine, Enyacho 89-1, Izumo, Shimane 6938501, Japan. kn88@med.shimane-u.ac.jp.
Abstract:
In this study, we examined the clinical significance of KRAS and MAPK1 amplification and assessed whether these amplified genes were potential therapeutic targets in type II ovarian carcinoma. Using fluorescence in situ hybridization, immunohistochemistry, and retrospectively collected clinical data, KRAS and MAPK1 amplifications were identified in 9 (13.2%) and 5 (7.4%) of 68 type II ovarian carcinoma tissue samples, respectively. Interestingly, co-amplification of KRAS and MAPK1 seemed to be absent in the type II ovarian carcinomas tested, except one case. Active phospho-ERK1/2 was identified in 26 (38.2%) out of 68 type II ovarian carcinomas and did not correlate with KRAS or MAPK1 amplification. There was no significant relationship between KRAS amplification and overall or progression-free survival in patients with type II ovarian carcinoma. However, patients with MAPK1 amplification had significantly poorer progression-free survival than patients without MAPK1 amplification. Moreover, type II ovarian carcinoma cells with concomitant KRAS amplification and mutation exhibited dramatic growth reduction following treatment with the MEK inhibitor PD0325901. These findings indicate that KRAS/MAPK1 amplification is critical for the growth of a subset of type II ovarian carcinomas. Additionally, RAS/RAF/MEK/ERK pathway-targeted therapy may benefit selected patients with type II ovarian carcinoma harboring KRAS/MAPK1 amplifications.
Insights
KRAS and MAPK1 gene amplification is significant in type II ovarian carcinoma. Targeting the RAS/RAF/MEK/ERK pathway may benefit patients with these specific gene amplifications.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Type II ovarian carcinoma is a complex disease with limited targeted therapies.
- KRAS and MAPK1 gene amplifications are potential drivers of tumor growth.
- Understanding these genetic alterations is crucial for developing novel treatment strategies.
Purpose of the Study:
- To investigate the clinical significance of KRAS and MAPK1 amplification in type II ovarian carcinoma.
- To evaluate KRAS and MAPK1 as potential therapeutic targets.
- To explore the correlation between gene amplification, pathway activation, and patient survival.
Main Methods:
- Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were used to detect gene amplifications.
- Retrospective clinical data from 68 type II ovarian carcinoma patients were analyzed.
- Analysis included correlation with phospho-ERK1/2 levels and patient survival outcomes.
Main Results:
- KRAS amplification was found in 13.2% and MAPK1 amplification in 7.4% of samples.
- No significant correlation was observed between KRAS/MAPK1 amplification and phospho-ERK1/2 levels.
- MAPK1 amplification was associated with significantly poorer progression-free survival.
Conclusions:
- KRAS and MAPK1 amplification are present in a subset of type II ovarian carcinomas and are critical for tumor growth.
- Targeted therapy inhibiting the RAS/RAF/MEK/ERK pathway, such as MEK inhibitors, shows promise for patients with KRAS/MAPK1 amplifications.
- These findings suggest a potential new therapeutic strategy for selected ovarian cancer patients.
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