Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer
Details
Publication Year 2024-07-18,Volume 15,Issue #1,Page 6069
Journal Title
Nature Communications
Publication Type
Research article
Abstract
Whole genome duplication is frequently observed in cancer, and its prevalence in our prior analysis of end-stage, homologous recombination deficient high grade serous ovarian cancer (almost 80% of samples) supports the notion that whole genome duplication provides a fitness advantage under the selection pressure of therapy. Here, we therefore aim to identify potential therapeutic vulnerabilities in primary high grade serous ovarian cancer with whole genome duplication by assessing differentially expressed genes and pathways in 79 samples. We observe that MHC-II expression is lowest in tumors which have acquired whole genome duplication early in tumor evolution, and further demonstrate that reduced MHC-II expression occurs in subsets of tumor cells rather than in canonical antigen-presenting cells. Early whole genome duplication is also associated with worse patient survival outcomes. Our results suggest an association between the timing of whole genome duplication, MHC-II expression and clinical outcome in high grade serous ovarian cancer that warrants further investigation for therapeutic targeting.
Publisher
Springer Nature
Keywords
Female; *Ovarian Neoplasms/genetics/pathology; Humans; *Cystadenocarcinoma, Serous/genetics/pathology; Gene Expression Regulation, Neoplastic; Gene Duplication; Genome, Human; Histocompatibility Antigens Class II/genetics/metabolism
Department(s)
Laboratory Research
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-024-50137-y
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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