PREreview of Genomic landscape of endometrial, ovarian and cervical cancers in Japan from database in the Center for Cancer Genomics and Advanced Therapeutics

Genomic Landscape of Endometrial, Ovarian and  Cervical Cancers in Japan from database in the Center for Cancer Genomics and Advanced Therapeutics

“A review of a preprint article published on medRxiv on the 9th of October 2023 which is accessible here. By Seun Olufemi and Femi Arogundade - PREreview Champions ’24. The methods (structured questions) used in this peer review were adapted from the PREreview  Open Reviewers training workshop for the PREreview Champions Program.”

Summary  

The study on gynecological cancers in Japan conducted a comprehensive genomic analysis using data from the C-CAT database, revealing significant insights into the mutational landscape of endometrial, ovarian, and cervical cancers. The study identified prevalent mutations such as TP53, PIK3CA, PTEN, KRAS, and BRCA1/2 across different cancer types and highlighted the varying mutation patterns among histological subtypes. The study underscored the high prevalence of TP53 mutations across all three cancer types and the utility of FoundationOne® CDx for detailed genomic profiling. These findings have potential implications for clinical decision-making and the development of targeted therapies in Japan and beyond. However, the retrospective nature of the study and inherent limitations of retrospective designs, including reliance on existing data and potential biases, should be considered in interpreting the results. Future research directions include longitudinal studies to track genetic changes over time and investigations into rare mutations and gene fusions that may contribute to gynecological cancers. Here, we list major and minor concerns that were discussed by participants of the Live Review, and, where possible, we provide suggestions on how to address those issues.

List of major issues and feedback 

• The authors should provide more detailed analysis by histological subtype to elucidate subtype-specific genomic profiles and potential therapeutic targets unique to each subtype.

• Expand on the clinical implications of the findings, particularly how specific mutations might impact treatment selection, prognosis, or resistance to therapy.

• The authors should specify the range or mean age of the patients included in the study.

• The authors should provide a rationale for these exclusions and discuss how they might impact the study's representativeness. Consider alternative approaches to include these cases or analyze the potential biases introduced by their exclusion.

• A detailed discussion on data quality control measures and any steps taken to address potential inaccuracies or missing data. Highlight how these limitations might affect the study’s conclusions

• An analysis of potential confounding factors and describe methods used to control for these variables. This could involve stratified analyses or multivariate modeling to account for these factors.

List of minor issues and feedback 

• The authors should provide detailed information about the bioinformatics pipelines, software versions, and parameters used in the analyses. This will enhance the reproducibility of the study.

• Add more comprehensive legends or annotations to these figures to help readers understand the data presented. Supplementary materials with expanded explanations could also be beneficial

Concluding remarks

We thank the authors of the preprint for posting their work openly for feedback. We also appreciate the efforts of Vanessa Fairhurst, for her feedback on this review. 

Conflict of Interest

No conflicts of interest were disclosed.

Competing interests

The authors declare that they have no competing interests.

Competing interests

The authors declare that they have no competing interests.