Related Experiment Video
Updated: May 6, 2026
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
Homologous recombination deficiency gene panel analysis results in synchronous endometrial and ovarian cancers
Ferah Kazanci1, Zerrin Yılmaz Çelik2, Mert Polat2
1Gazi University, Faculty of Medicine, Department of Gynaecologic Oncology - Ankara, Turkey.
Objective:
The objective of this study was to analyze the genetic alterations of tumors within the scope of the homologous recombination deficiency gene panel in patients diagnosed with synchronous endometrial ovarian cancer who have been followed for over 5 years using next-generation sequencing.
Methods:
DNA was isolated from the patient's formalin-fixed, paraffin-embedded tissue blocks. Next-generation sequencing was performed using the Illumina capture-based sequencing method. Samples were sequenced using the Sophia HR Solution DNA Kit.
Results:
Seven patients were included in this study. The ratios of likely pathogenic (LP)/pathogenic (P) somatic mutations in ATM (serine/threonine kinase or Ataxia-telangiectasia mutated gene), BRCA2 (breast cancer type 2 susceptibility gene), BARD1 (BRCA1 associated RING domain 1), TP53 (tumor protein p53), BIRP1 (BRCA1-interacting helicase 1 gene), PALB2 (partner and localizer of BRCA2), and CHECK2 were 21 (48.8%), 8 (18.6%), 5 (11.6%), 3 (6.9%), 2 (4.6%), 2 (4.6%), and 2 (4.6%), respectively, in endometrium, and the ratios of somatic mutations in ATM, BRCA2, TP53, BARD1, RAD54L (DNA repair/recombination protein like), BIRP1, and RAD51D (RAD51 recombinase paralog D) were 24 (60%), 6 (15%), 5 (12.5%), 2 (5%), 2 (5%), 1 (2.5%), and 1 (2.5%), respectively, in ovary. In endometrioid-synchronous endometrial ovarian cancer cases, P/LP mutations were observed in ATM and CHECK2 genes in endometrium and ATM, BRCA2, and TP53 genes in ovary. In two non-endometrioid-synchronous endometrial ovarian cancer cases, CHEK2 (checkpoint kinase 2) mutations were observed in endometrium and ATM and TP53 mutations in ovary, whereas in one case, P/LP mutations in ATM and TP53 genes were common in both tissues.
Conclusion:
Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.
Insights
Genetic analysis of synchronous endometrial ovarian cancer revealed common mutations in the ATM gene. This finding suggests ATM alterations may be linked to a better prognosis in these patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Synchronous endometrial and ovarian cancers present a diagnostic and therapeutic challenge.
- Understanding the genetic landscape of these synchronous tumors is crucial for targeted therapies.
Purpose of the Study:
- To investigate genetic alterations in synchronous endometrial ovarian cancer using a homologous recombination deficiency (HRD) gene panel.
- To identify common mutations and their potential prognostic significance in a cohort followed for over 5 years.
Main Methods:
- Next-generation sequencing (NGS) was employed to analyze DNA from formalin-fixed, paraffin-embedded tissues.
- A comprehensive HRD gene panel, including genes like ATM, BRCA2, and TP53, was utilized.
- Illumina capture-based sequencing and the Sophia HR Solution DNA Kit were used for sample analysis.
Main Results:
- ATM gene mutations were the most frequent alteration, observed in 48.8% of endometrial and 60% of ovarian samples.
- Pathogenic/likely pathogenic mutations were identified in ATM, BRCA2, TP53, BARD1, BIRP1, PALB2, and CHEK2 across both tumor types.
- ATM and TP53 mutations were frequently found in both endometrial and ovarian components, particularly in non-endometrioid subtypes.
Conclusions:
- Genetic alterations were detected in nearly all patients, confirming the diagnosis of synchronous endometrial ovarian cancer.
- ATM gene mutations are a prevalent finding and may be associated with a favorable prognosis.
- Targeted gene panel sequencing provides valuable insights into the molecular basis of synchronous endometrial ovarian cancer.
