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Ref Type Journal Article
PMID (24563622)
Authors Martignetti JA, Camacho-Vanegas O, Priedigkeit N, Camacho C, Pereira E, Lin L, Garnar-Wortzel L, Miller D, Losic B, Shah H, Liao J, Ma J, Lahiri P, Chee M, Schadt E, Dottino P
Title Personalized ovarian cancer disease surveillance and detection of candidate therapeutic drug target in circulating tumor DNA.
Journal Neoplasia (New York, N.Y.)
Vol 16
Issue 1
Date 2014 Jan
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FGFR2 FAM76A FGFR2 - FAM76A fusion gain of function - predicted FGFR2-FAM76A results from the fusion of FGFR2 and FAM76A, which leads to increased proliferation and transformation in cell culture (PMID: 24563622), and therefore, is predicted to result in a gain of protein function. FGFR2-FAM76A has been identified in ovarian cancer (PMID: 24563622).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 - FAM76A ovarian cancer sensitive Infigratinib Preclinical - Patient cell culture Actionable In a preclincal study, Truseltiq (infigratinib) demonstrated enhanced inhibition of the survival in patient-derived ovarian cancer cells harboring FGFR2 - FAM76A in culture (PMID: 24563622). 24563622