Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures
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 potentia...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/20/5242 |
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| author | Douglas V. N. P. Oliveira Tine H. Schnack Tim S. Poulsen Anne P. Christiansen Claus K. Høgdall Estrid V. Høgdall |
| author_facet | Douglas V. N. P. Oliveira Tine H. Schnack Tim S. Poulsen Anne P. Christiansen Claus K. Høgdall Estrid V. Høgdall |
| author_sort | Douglas V. N. P. Oliveira |
| collection | DOAJ |
| description | 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, <i>ARID1A</i> and <i>PIK3CA</i> were the most prevalent mutations, present in 49.1% and 41.8%, respectively. From those, the co-occurrence of <i>ARID1A</i> and <i>PIK3CA</i> 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 <i>ARID1A</i> and <i>PIK3CA</i> double mutation) subgroups exhibited unique signatures, whilst “ARID1A” and “Undetermined” (no mutations on <i>ARID1A</i> nor <i>PIK3CA</i>) 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. |
| first_indexed | 2024-03-10T06:40:48Z |
| format | Article |
| id | doaj.art-bd559f9ff4a84b32a5674fb578edf971 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:40:48Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bd559f9ff4a84b32a5674fb578edf9712023-11-22T17:42:35ZengMDPI AGCancers2072-66942021-10-011320524210.3390/cancers13205242Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational SignaturesDouglas V. N. P. Oliveira0Tine H. Schnack1Tim S. Poulsen2Anne P. Christiansen3Claus K. Høgdall4Estrid V. Høgdall5Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, DenmarkDepartment of Gynecology, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, DenmarkMolecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, DenmarkDepartment of Pathology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, DenmarkDepartment of Gynecology, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, DenmarkMolecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, DenmarkOvarian 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, <i>ARID1A</i> and <i>PIK3CA</i> were the most prevalent mutations, present in 49.1% and 41.8%, respectively. From those, the co-occurrence of <i>ARID1A</i> and <i>PIK3CA</i> 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 <i>ARID1A</i> and <i>PIK3CA</i> double mutation) subgroups exhibited unique signatures, whilst “ARID1A” and “Undetermined” (no mutations on <i>ARID1A</i> nor <i>PIK3CA</i>) 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.https://www.mdpi.com/2072-6694/13/20/5242ovarian cancerclear cell carcinomapatient stratificationmutational signatureNGSgenomic instability |
| spellingShingle | Douglas V. N. P. Oliveira Tine H. Schnack Tim S. Poulsen Anne P. Christiansen Claus K. Høgdall Estrid V. Høgdall Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures Cancers ovarian cancer clear cell carcinoma patient stratification mutational signature NGS genomic instability |
| title | Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures |
| title_full | Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures |
| title_fullStr | Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures |
| title_full_unstemmed | Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures |
| title_short | Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures |
| title_sort | genomic sub classification of ovarian clear cell carcinoma revealed by distinct mutational signatures |
| topic | ovarian cancer clear cell carcinoma patient stratification mutational signature NGS genomic instability |
| url | https://www.mdpi.com/2072-6694/13/20/5242 |
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