Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies
Abstract Plasma circulating tumour DNA (ctDNA) has been suggested to be a viable biomarker of response to treatment in patients with high grade serous ovarian carcinoma (HGSOC). TP53 mutations are present in more than 90% of HGSOCs but somatic variants are distributed across all exonic regions of th...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-27445-2 |
| _version_ | 1797958703318564864 |
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| author | Leslie Calapre Tindaro Giardina Aaron B. Beasley Anna L. Reid Colin Stewart Benhur Amanuel Tarek M. Meniawy Elin S. Gray |
| author_facet | Leslie Calapre Tindaro Giardina Aaron B. Beasley Anna L. Reid Colin Stewart Benhur Amanuel Tarek M. Meniawy Elin S. Gray |
| author_sort | Leslie Calapre |
| collection | DOAJ |
| description | Abstract Plasma circulating tumour DNA (ctDNA) has been suggested to be a viable biomarker of response to treatment in patients with high grade serous ovarian carcinoma (HGSOC). TP53 mutations are present in more than 90% of HGSOCs but somatic variants are distributed across all exonic regions of the gene, requiring next generation sequencing (NGS) technologies for mutational analysis. In this study, we compared the suitability of the Accel (Swift) and Oncomine (ThermoFisher) panels for identification of TP53 mutations in ctDNA of HGSOC patients (N = 10). Only 6 patients (60%) were found to have TP53 mutations using the ACCEL panel but the addition of molecular tags in the Oncomine panel improved ctDNA detection with at least one mutation detected in all cases (100%). Orthogonal validation of the 14 somatic variants found by Oncomine, using droplet digital PCR, confirmed 79% (11/14) of the identified mutations. Overall, the Oncomine panel with unique molecular identifiers (UMI) appears more useful for ctDNA analysis in HGSOC. |
| first_indexed | 2024-04-11T00:22:45Z |
| format | Article |
| id | doaj.art-4563136ea8714a7294842de73f101b88 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T00:22:45Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-4563136ea8714a7294842de73f101b882023-01-08T12:09:44ZengNature PortfolioScientific Reports2045-23222023-01-011311710.1038/s41598-023-27445-2Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologiesLeslie Calapre0Tindaro Giardina1Aaron B. Beasley2Anna L. Reid3Colin Stewart4Benhur Amanuel5Tarek M. Meniawy6Elin S. Gray7School of Medical and Health Sciences, Edith Cowan UniversityAnatomical Pathology, PathWest Laboratory Medicine, QEII Medical CentreSchool of Medical and Health Sciences, Edith Cowan UniversitySchool of Medical and Health Sciences, Edith Cowan UniversityAnatomical Pathology, PathWest Laboratory Medicine, QEII Medical CentreSchool of Medical and Health Sciences, Edith Cowan UniversitySchool of Medical and Health Sciences, Edith Cowan UniversitySchool of Medical and Health Sciences, Edith Cowan UniversityAbstract Plasma circulating tumour DNA (ctDNA) has been suggested to be a viable biomarker of response to treatment in patients with high grade serous ovarian carcinoma (HGSOC). TP53 mutations are present in more than 90% of HGSOCs but somatic variants are distributed across all exonic regions of the gene, requiring next generation sequencing (NGS) technologies for mutational analysis. In this study, we compared the suitability of the Accel (Swift) and Oncomine (ThermoFisher) panels for identification of TP53 mutations in ctDNA of HGSOC patients (N = 10). Only 6 patients (60%) were found to have TP53 mutations using the ACCEL panel but the addition of molecular tags in the Oncomine panel improved ctDNA detection with at least one mutation detected in all cases (100%). Orthogonal validation of the 14 somatic variants found by Oncomine, using droplet digital PCR, confirmed 79% (11/14) of the identified mutations. Overall, the Oncomine panel with unique molecular identifiers (UMI) appears more useful for ctDNA analysis in HGSOC.https://doi.org/10.1038/s41598-023-27445-2 |
| spellingShingle | Leslie Calapre Tindaro Giardina Aaron B. Beasley Anna L. Reid Colin Stewart Benhur Amanuel Tarek M. Meniawy Elin S. Gray Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies Scientific Reports |
| title | Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies |
| title_full | Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies |
| title_fullStr | Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies |
| title_full_unstemmed | Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies |
| title_short | Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies |
| title_sort | identification of tp53 mutations in circulating tumour dna in high grade serous ovarian carcinoma using next generation sequencing technologies |
| url | https://doi.org/10.1038/s41598-023-27445-2 |
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