Genomic sub-classification of ovarian clear cell carcinoma revealed by distinct mutational signatures

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Ovarian clear cell carcinoma (OCCC) is characterized by dismal prognosis, partially due to its low sensitivity to standard chemotherapy regimen. It is also well-known for presenting unique molecular features in comparison to other epithelial ovarian cancer subtypes. Here, we aim to identify potential subgroups of patients in order to (1) determine their molecular features and (2) characterize their mutational signature. Furthermore, we sought to perform the investigation based on a potentially clinically relevant setting. To that end, we assessed the mutational profile and genomic instability of 55 patients extracted from the Gynecologic Cancer Database (DGCD) by using a panel comprised of 409 cancer-associated genes and a microsatellite assay, respectively; both are currently used in our routine environment. In accordance with previous findings, ARID1A and PIK3CA were the most prevalent mutations, present in 49.1% and 41.8%, respectively. From those, the co-occurrence of ARID1A and PIK3CA mutations was observed in 36.1% of subjects, indicating that this association might be a common feature of OCCC. The microsatellite instability frequency was low across samples. An unbiased assessment of signatures identified the presence of three subgroups, where “PIK3CA” and “Double hit” (with ARID1A and PIK3CA double mutation) subgroups exhibited unique signatures, whilst “ARID1A” and “Undetermined” (no mutations on ARID1A nor PIK3CA) subgroups showed similar profiles. Those differences were further indicated by COSMIC signatures. Taken together, the current findings suggest that OCCC presents distinct mutational landscapes within its group, which may indicate different therapeutic approaches according to its subgroup. Although encouraging, it is noteworthy that the current results are limited by sample size, and further investigation on a larger group would be crucial to better elucidate them.

OriginalsprogEngelsk
Artikelnummer5242
TidsskriftCancers
Vol/bind13
Udgave nummer20
Antal sider14
ISSN2072-6694
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
The study was supported by the Mermaid Foundation, Danish Cancer Research Foundation and Herlev Hospital Research Council. Funding sources had no influence in any part of the study. The authors thank the Danish Gynecological Cancer Group (www.http:// www.dgcg.dk/ (accessed on 20 August 2021)) and the Bio-and Genome Bank Denmark (https: //www.regioner.dk/ (accessed on 20 August 2021)) for providing with the biological samples and data registry, and Christina Gr?nh?j, Lone S. Dupont, Wojciech Skovrider-Ruminski and Guy W. Novotny for their technical support and expertise.

Funding Information:
Funding: The study was supported by the Mermaid Foundation, Danish Cancer Research Foundation and Herlev Hospital Research Council. Funding sources had no influence in any part of the study.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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