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Open AccessArticle

New Challenges in Tumor Mutation Heterogeneity in Advanced Ovarian Cancer by a Targeted Next-Generation Sequencing (NGS) Approach

1
Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 Aviano, Italy
2
Scientific Directorate, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 Aviano, Italy
3
Medical Oncology, “Santa Maria della Misericordia” University Hospital, ASUIUD, 33100 Udine, Italy
4
Medical Oncology Unit C, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 Aviano, Italy
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Pathology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 Aviano, Italy
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Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy
7
Gynecological Oncology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, 33081 Aviano, Italy
*
Author to whom correspondence should be addressed.
E. Cecchin and G. Toffoli share last authorship.
Cells 2019, 8(6), 584; https://doi.org/10.3390/cells8060584
Received: 20 May 2019 / Revised: 6 June 2019 / Accepted: 13 June 2019 / Published: 14 June 2019
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Ovarian Cancer)
Next-generation sequencing (NGS) technology has advanced knowledge of the genomic landscape of ovarian cancer, leading to an innovative molecular classification of the disease. However, patient survival and response to platinum-based treatments are still not predictable based on the tumor genetic profile. This retrospective study characterized the repertoire of somatic mutations in advanced ovarian cancer to identify tumor genetic markers predictive of platinum chemo-resistance and prognosis. Using targeted NGS, 79 primary advanced (III–IV stage, tumor grade G2-3) ovarian cancer tumors, including 64 high-grade serous ovarian cancers (HGSOCs), were screened with a 26 cancer-genes panel. Patients, enrolled between 1995 and 2011, underwent primary debulking surgery (PDS) with optimal residual disease (RD < 1 cm) and platinum-based chemotherapy as first-line treatment. We found a heterogeneous mutational landscape in some uncommon ovarian histotypes and in HGSOC tumor samples with relevance in predicting platinum sensitivity. In particular, we identified a poor prognostic signature in patients with HGSOC harboring concurrent mutations in two driver actionable genes of the panel. The tumor heterogeneity described, sheds light on the translational potential of targeted NGS approach for the identification of subgroups of patients with distinct therapeutic vulnerabilities, that are modulated by the specific mutational profile expressed by the ovarian tumor. View Full-Text
Keywords: advanced ovarian cancer; HGSOC; NGS; tumor profile; concurrent somatic mutations; TP53; platinum sensitivity; driver actionable genes; translational medicine advanced ovarian cancer; HGSOC; NGS; tumor profile; concurrent somatic mutations; TP53; platinum sensitivity; driver actionable genes; translational medicine
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Garziera, M.; Roncato, R.; Montico, M.; De Mattia, E.; Gagno, S.; Poletto, E.; Scalone, S.; Canzonieri, V.; Giorda, G.; Sorio, R.; Cecchin, E.; Toffoli, G. New Challenges in Tumor Mutation Heterogeneity in Advanced Ovarian Cancer by a Targeted Next-Generation Sequencing (NGS) Approach. Cells 2019, 8, 584.

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