Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA
Retrospective studies have demonstrated that nearly 50% of patients with ovarian cancer with normal cancer antigen 125 (CA125) levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here, we demonstrate that for one patient, with the first rep...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558614800092 |
| _version_ | 1828553063685685248 |
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| author | John A. Martignetti Olga Camacho-Vanegas Nolan Priedigkeit Catalina Camacho Elena Pereira Li Lin Leopold Garnar-Wortzel Dagny Miller Bojan Losic Hardik Shah Jun Liao Jian Ma Pratik Lahiri Mark Chee Eric Schadt Peter Dottino |
| author_facet | John A. Martignetti Olga Camacho-Vanegas Nolan Priedigkeit Catalina Camacho Elena Pereira Li Lin Leopold Garnar-Wortzel Dagny Miller Bojan Losic Hardik Shah Jun Liao Jian Ma Pratik Lahiri Mark Chee Eric Schadt Peter Dottino |
| author_sort | John A. Martignetti |
| collection | DOAJ |
| description | Retrospective studies have demonstrated that nearly 50% of patients with ovarian cancer with normal cancer antigen 125 (CA125) levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here, we demonstrate that for one patient, with the first reported fibroblast growth factor receptor 2 (FGFR2) fusion transcript in ovarian cancer, circulating tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125, and it can also inform on a candidate therapeutic. For a 4-year period, during which the patient underwent primary debulking surgery and chemotherapy, tumor recurrences, and multiple chemotherapeutic regimens, blood samples were longitudinally collected and stored. Whereas postsurgical CA125 levels were elevated only three times for 28 measurements, the FGFR2 fusion ctDNA biomarker was readily detectable by quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all of these same blood samples and in the tumor recurrences. Given the persistence of the FGFR2 fusion, we treated tumor cells derived from this patient and others with the FGFR2 inhibitor BGJ398. Only tumor cells derived from this patient were sensitive to FGFR2 inhibitor treatment. Using the same methodologic approach, we demonstrate in a second patient with a different fusion that PCR and agarose gel electrophoresis can also be used to identify tumor-specific DNA in the circulation. Taken together, we demonstrate that a relatively inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in identifying occult disease. |
| first_indexed | 2024-12-12T05:12:16Z |
| format | Article |
| id | doaj.art-e663291f25024bdbb6f4e397597a489e |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-12T05:12:16Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-e663291f25024bdbb6f4e397597a489e2022-12-22T00:36:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022014-01-011619710310.1593/neo.131900Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNAJohn A. Martignetti0Olga Camacho-Vanegas1Nolan Priedigkeit2Catalina Camacho3Elena Pereira4Li Lin5Leopold Garnar-Wortzel6Dagny Miller7Bojan Losic8Hardik Shah9Jun Liao10Jian Ma11Pratik Lahiri12Mark Chee13Eric Schadt14Peter Dottino15Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, ILDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, ILPrognosys Biosciences, San Diego, CADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NYDepartment of Obstetrics/Gynecology and Reproductive Sciences, Icahn School of Medicine at Mount Sinai, New York, NYRetrospective studies have demonstrated that nearly 50% of patients with ovarian cancer with normal cancer antigen 125 (CA125) levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here, we demonstrate that for one patient, with the first reported fibroblast growth factor receptor 2 (FGFR2) fusion transcript in ovarian cancer, circulating tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125, and it can also inform on a candidate therapeutic. For a 4-year period, during which the patient underwent primary debulking surgery and chemotherapy, tumor recurrences, and multiple chemotherapeutic regimens, blood samples were longitudinally collected and stored. Whereas postsurgical CA125 levels were elevated only three times for 28 measurements, the FGFR2 fusion ctDNA biomarker was readily detectable by quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all of these same blood samples and in the tumor recurrences. Given the persistence of the FGFR2 fusion, we treated tumor cells derived from this patient and others with the FGFR2 inhibitor BGJ398. Only tumor cells derived from this patient were sensitive to FGFR2 inhibitor treatment. Using the same methodologic approach, we demonstrate in a second patient with a different fusion that PCR and agarose gel electrophoresis can also be used to identify tumor-specific DNA in the circulation. Taken together, we demonstrate that a relatively inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in identifying occult disease.http://www.sciencedirect.com/science/article/pii/S1476558614800092 |
| spellingShingle | John A. Martignetti Olga Camacho-Vanegas Nolan Priedigkeit Catalina Camacho Elena Pereira Li Lin Leopold Garnar-Wortzel Dagny Miller Bojan Losic Hardik Shah Jun Liao Jian Ma Pratik Lahiri Mark Chee Eric Schadt Peter Dottino Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA Neoplasia: An International Journal for Oncology Research |
| title | Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA |
| title_full | Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA |
| title_fullStr | Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA |
| title_full_unstemmed | Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA |
| title_short | Personalized Ovarian Cancer Disease Surveillance and Detection of Candidate Therapeutic Drug Target in Circulating Tumor DNA |
| title_sort | personalized ovarian cancer disease surveillance and detection of candidate therapeutic drug target in circulating tumor dna |
| url | http://www.sciencedirect.com/science/article/pii/S1476558614800092 |
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