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Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients

Genetic testing to detect somatic alterations is usually performed on formalin-fixed paraffin-embedded tumor samples. However, tumor molecular profiling through ctDNA analysis may be particularly interesting with the emergence of targeted therapies for ovarian cancer (OC), mainly when tumor is not a...

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Autores principales: Barbosa, Ana, Pinto, Pedro, Peixoto, Ana, Guerra, Joana, Pinheiro, Manuela, Santos, Catarina, Pinto, Carla, Escudeiro, Carla, Bartosch, Carla, Santos, Rui, Brandão, Andreia, Silva, João, Teixeira, Manuel R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515058/
https://www.ncbi.nlm.nih.gov/pubmed/34660321
http://dx.doi.org/10.3389/fonc.2021.754094
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author Barbosa, Ana
Pinto, Pedro
Peixoto, Ana
Guerra, Joana
Pinheiro, Manuela
Santos, Catarina
Pinto, Carla
Escudeiro, Carla
Bartosch, Carla
Santos, Rui
Brandão, Andreia
Silva, João
Teixeira, Manuel R.
author_facet Barbosa, Ana
Pinto, Pedro
Peixoto, Ana
Guerra, Joana
Pinheiro, Manuela
Santos, Catarina
Pinto, Carla
Escudeiro, Carla
Bartosch, Carla
Santos, Rui
Brandão, Andreia
Silva, João
Teixeira, Manuel R.
author_sort Barbosa, Ana
collection PubMed
description Genetic testing to detect somatic alterations is usually performed on formalin-fixed paraffin-embedded tumor samples. However, tumor molecular profiling through ctDNA analysis may be particularly interesting with the emergence of targeted therapies for ovarian cancer (OC), mainly when tumor is not available and biopsy is not viable, also allowing representation of multiple neoplastic subclones. Using a custom panel of 27 genes, next-generation sequencing (NGS) was performed on tumor and matched plasma samples from 96 OC patients, which were combined in two groups (treatment naive and post-treatment). Overall, at least one somatic variant present in the tumor sample was also detected in the matched plasma sample in 35.6% of the patients, a percentage that increased to 69.6% of the treatment naive patients and 83.3% of those with stage IV disease, showing the potential of ctDNA analysis as an alternative to identify somatic variants in these patients, namely those that have predictive value for targeted therapy. In fact, of the two treatment-naive patients with somatic BRCA1 variants identified in tumor samples, in one of them we detected in ctDNA a BRCA1 somatic variant that was present in the tumor with a VAF of 53%, but not in the one that had a VAF of 5.4%. We also showed that ctDNA analysis has a complementary role to molecular unraveling of inter- and intra-tumor heterogeneity, as exemplified by one patient diagnosed with bilateral OC in which different somatic variants from both tumors were detected in ctDNA. Interestingly, as these bilateral tumors shared a rare combination of two of the three variants identified in ctDNA, we could conclude that these morphologically different tumors were clonally related and not synchronous independent neoplasias. Moreover, in the post-treatment group of patients with plasma samples collected after surgery, those with detectable somatic variants had poor prognosis when compared with patients with no detectable somatic variants, highlighting the potential of ctDNA analysis to identify patients at higher risk of recurrence. Concluding, this study demonstrated that somatic variants can be detected in plasma samples of a significant proportion of OC patients, supporting the use of NGS-based ctDNA testing for noninvasive tumor molecular profiling and to stratify patients according to prognosis.
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spelling pubmed-85150582021-10-15 Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients Barbosa, Ana Pinto, Pedro Peixoto, Ana Guerra, Joana Pinheiro, Manuela Santos, Catarina Pinto, Carla Escudeiro, Carla Bartosch, Carla Santos, Rui Brandão, Andreia Silva, João Teixeira, Manuel R. Front Oncol Oncology Genetic testing to detect somatic alterations is usually performed on formalin-fixed paraffin-embedded tumor samples. However, tumor molecular profiling through ctDNA analysis may be particularly interesting with the emergence of targeted therapies for ovarian cancer (OC), mainly when tumor is not available and biopsy is not viable, also allowing representation of multiple neoplastic subclones. Using a custom panel of 27 genes, next-generation sequencing (NGS) was performed on tumor and matched plasma samples from 96 OC patients, which were combined in two groups (treatment naive and post-treatment). Overall, at least one somatic variant present in the tumor sample was also detected in the matched plasma sample in 35.6% of the patients, a percentage that increased to 69.6% of the treatment naive patients and 83.3% of those with stage IV disease, showing the potential of ctDNA analysis as an alternative to identify somatic variants in these patients, namely those that have predictive value for targeted therapy. In fact, of the two treatment-naive patients with somatic BRCA1 variants identified in tumor samples, in one of them we detected in ctDNA a BRCA1 somatic variant that was present in the tumor with a VAF of 53%, but not in the one that had a VAF of 5.4%. We also showed that ctDNA analysis has a complementary role to molecular unraveling of inter- and intra-tumor heterogeneity, as exemplified by one patient diagnosed with bilateral OC in which different somatic variants from both tumors were detected in ctDNA. Interestingly, as these bilateral tumors shared a rare combination of two of the three variants identified in ctDNA, we could conclude that these morphologically different tumors were clonally related and not synchronous independent neoplasias. Moreover, in the post-treatment group of patients with plasma samples collected after surgery, those with detectable somatic variants had poor prognosis when compared with patients with no detectable somatic variants, highlighting the potential of ctDNA analysis to identify patients at higher risk of recurrence. Concluding, this study demonstrated that somatic variants can be detected in plasma samples of a significant proportion of OC patients, supporting the use of NGS-based ctDNA testing for noninvasive tumor molecular profiling and to stratify patients according to prognosis. Frontiers Media S.A. 2021-09-30 /pmc/articles/PMC8515058/ /pubmed/34660321 http://dx.doi.org/10.3389/fonc.2021.754094 Text en Copyright © 2021 Barbosa, Pinto, Peixoto, Guerra, Pinheiro, Santos, Pinto, Escudeiro, Bartosch, Santos, Brandão, Silva and Teixeira https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Barbosa, Ana
Pinto, Pedro
Peixoto, Ana
Guerra, Joana
Pinheiro, Manuela
Santos, Catarina
Pinto, Carla
Escudeiro, Carla
Bartosch, Carla
Santos, Rui
Brandão, Andreia
Silva, João
Teixeira, Manuel R.
Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients
title Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients
title_full Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients
title_fullStr Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients
title_full_unstemmed Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients
title_short Next Generation Sequencing of Tumor and Matched Plasma Samples: Identification of Somatic Variants in ctDNA From Ovarian Cancer Patients
title_sort next generation sequencing of tumor and matched plasma samples: identification of somatic variants in ctdna from ovarian cancer patients
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515058/
https://www.ncbi.nlm.nih.gov/pubmed/34660321
http://dx.doi.org/10.3389/fonc.2021.754094
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