scholarly journals A rare case of recurrent ovarian cancer with NTRK1-TPM3 gene rearrangement

2021 ◽  
Author(s):  
Yuta Endo ◽  
Takafumi Watanabe ◽  
Motonobu Saito ◽  
Katsuharu Saito ◽  
Rei Suzuki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Fusion ◽  
Rare Case ◽  
Multimodal Therapy ◽  
Gynecologic Cancer ◽  
Stage Iv ◽  
Recurrent Ovarian Cancer ◽  
Interval Debulking Surgery ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: NTRK gene fusion is rare in gynecologic cancer. Entrectinib is a novel targeted drug which is a potent inhibitor of TRK A, B and C. Here, we present a case of recurrent ovarian cancer with NTRK1-TPM3 rearrangement, which was detected by next-generation sequencing (NGS) and treated with entrectinib. Case Presentation:A 56-year-old woman was diagnosed as having stage IV ovarian cancer due to pleural effusion. Neoadjuvant chemotherapy and interval debulking surgery followed by chemotherapy were performed. Ten months after completion of chemotherapy, the patient’s disease recurred. She was treated with multimodal therapy for recurrence. DNA-based NGS detected NTRK1-TPM3 rearrangement and entrectinib was started. However, the patient’s disease progressed despite six weeks’ administration of entrectinib, and one month after discontinuation of entrectinib, she died. After her death immunohistochemistry with a pan-Trk monoclonal antibody was performed to determine the expression of NTRK. However, immunohistochemistry was negative for NTRK.Conclusion: We presented a rare case of recurrent ovarian cancer with NTRK1-TPM3 gene fusion, in which entrectinib was not effective. While NTRK gene fusion was detected by DNA-based NGS, immunohistochemistry was negative for NTRK. Immunohistchemitory should be performed for confirmation of NTRK protein expression before entrectinib administration.

scholarly journals A Rare Case of Recurrent Ovarian Cancer With NTRK1-TPM3 Gene Rearrangement

2021 ◽  
Author(s):  
Yuta Endo ◽  
Takafumi Watanabe ◽  
Motonobu Saito ◽  
Katsuharu Saito ◽  
Rei Suzuki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Fusion ◽  
Rare Case ◽  
Gynecologic Cancer ◽  
Stage Iv ◽  
Recurrent Ovarian Cancer ◽  
Case Presentation ◽  
Interval Debulking Surgery ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: NTRK gene fusion is rare in gynecologic cancer. Entrectinib is a novel targeted drug which is a potent inhibitor of TRK A, B and C. Here, we present a case of recurrent ovarian cancer with NTRK1-TPM3 rearrangement, which was detected by next-generation sequencing (NGS) and treated with entrectinib. Case Presentation: A 56-year-old woman was diagnosed as having stage IV ovarian cancer due to pleural effusion. Neoadjuvant chemotherapy and interval debulking surgery followed by chemotherapy were performed. Ten months after completion of chemotherapy, the patient’s disease recurred. She was treated with multimodal therapy for recurrence. DNA-based NGS detected NTRK1-TPM3 rearrangement and entrectinib was started. However, the patient’s disease progressed despite six weeks’ administration of entrectinib, and one month after discontinuation of entrectinib, she died. After her death immunohistochemistry with a pan-Trk monoclonal antibody was performed to determine the expression of TRK. However, immunohistochemistry was negative for TRK.Conclusion: We presented a rare case of recurrent ovarian cancer with NTRK1-TPM3 gene fusion, in which entrectinib was not effective. While NTRK gene fusion was detected by DNA-based NGS, immunohistochemistry was negative for TRK. Immunohistchemitory should be performed for confirmation of TRK protein expression before entrectinib administration.

scholarly journals Applications of Next Generation Sequencing to the Analysis of Familial Breast/Ovarian Cancer

2020 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Veronica Zelli ◽  
Chiara Compagnoni ◽  
Katia Cannita ◽  
Roberta Capelli ◽  
Carlo Capalbo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Brca1 And Brca2 ◽  
Familial Predisposition ◽  
Cancer Pathogenesis ◽  
Or Gene ◽  
Gene Panels ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Next generation sequencing (NGS) provides a powerful tool in the field of medical genetics, allowing one to perform multi-gene analysis and to sequence entire exomes (WES), transcriptomes or genomes (WGS). The generated high-throughput data are particularly suitable for enhancing the understanding of the genetic bases of complex, multi-gene diseases, such as cancer. Among the various types of tumors, those with a familial predisposition are of great interest for the isolation of novel genes or gene variants, detectable at the germline level and involved in cancer pathogenesis. The identification of novel genetic factors would have great translational value, helping clinicians in defining risk and prevention strategies. In this regard, it is known that the majority of breast/ovarian cases with familial predisposition, lacking variants in the highly penetrant BRCA1 and BRCA2 genes (non-BRCA), remains unexplained, although several less penetrant genes (e.g., ATM, PALB2) have been identified. In this scenario, NGS technologies offer a powerful tool for the discovery of novel factors involved in familial breast/ovarian cancer. In this review, we summarize and discuss the state of the art applications of NGS gene panels, WES and WGS in the context of familial breast/ovarian cancer.

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

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 584 ◽  
Author(s):  
Marica Garziera ◽  
Rossana Roncato ◽  
Marcella Montico ◽  
Elena De Mattia ◽  
Sara Gagno ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Genetic Profile ◽  
Next Generation ◽  
Platinum Based Chemotherapy ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

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.

Clinical Trials in Recurrent Ovarian Cancer

2011 ◽  
Vol 21 (4) ◽  
pp. 771-775 ◽  
Author(s):  
Michael Friedlander ◽  
Edward Trimble ◽  
Anna Tinker ◽  
David Alberts ◽  
Elisabeth Avall-Lundqvist ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Gynecologic Cancer ◽  
Recurrent Ovarian Cancer ◽  
Consensus Conference ◽  
Ca 125 ◽  
Therapeutic Approaches ◽  
Cooperative Research ◽  
International Consensus

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

scholarly journals Tumor BRCA testing in ovarian cancer and EQA scheme: our experience of a critical evaluation

2021 ◽  
Author(s):  
Elisa De Paolis ◽  
Paola Concolino ◽  
Maria Elisabetta Onori ◽  
Concetta Santonocito ◽  
Claudia Marchetti ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Biology ◽  
Critical Evaluation ◽  
Efficient System ◽  
Continuous Quality ◽  
Control Procedures ◽  
Molecular Biology Method ◽  
Next Generation Sequencing Ngs ◽  
Quality Assessments ◽  
Generation Sequencing

AbstractNext generation sequencing (NGS) is a widespread molecular biology method integrated into clinical practice to detect genetic variants, for diagnostic and prognostic purposes. The scheduled external quality assessments (EQA) is integral part of clinical molecular laboratory quality assurance. The EQA provides an efficient system to compare analytic test performances among different laboratories, which is essential to evaluate consistency of molecular test. EQA failures demands targeted corrective action plans. In this context, the complexity of the NGS techniques requires careful and continuous quality control procedures. We report a tumor BRCA1/2 (tBRCA) testing benchmark discrepancy provided by the European Molecular Genetics Quality Network in our laboratory during a round of EQA for somatic mutation testing of BRCA genes in relation to ovarian cancer. The critical analysis emerging from the tBRCA EQA is presented. We underline that harmonization processes are still required for the EQA in the molecular biology field, especially if applied to the evaluation of methods characterized by high complexity.

A phase II trial of combination irinotecan and oral etoposide chemotherapy in recurrent ovarian cancer: A Tohoku Gynecologic Cancer Unit (TGCU) study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5558-5558
Author(s):  
S. Kumagai ◽  
T. Shoji ◽  
Y. Yokoyama ◽  
T. Takano ◽  
H. Mizunuma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Treatment Options ◽  
Gynecologic Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Oral Etoposide ◽  
Eligibility Criteria ◽  
Platinum Resistant

5558 Background: Various problems still exist in the management of recurrent ovarian cancer and there are limited treatment options especially for the platinum resistant patients (pts). We conducted a phase II study to evaluate the efficacy and safety of the combination irinotecan/oral etoposide chemotherapy. Methods: Eligibility criteria included recurrent ovarian cancer with measurable disease or positive CA125, preserved organ function, and aged 20–75. Treatment was conducted with irinotecan (60 mg/m2 iv, day 1, 15) and oral etoposide (50 mg/body day 1–21), q 28 days until disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) and secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: 38pts were enrolled on this study from May 2003 to April 2007, and all pts were eligible. Median age was 57 yrs (range 37–74). PS 0 in 24 pts, 1 in 10 pts, and 2 in 4 pts. Median number of previous regimen was 2 (range 1–4). Median treatment cycles were 6 (range 2–27). RR (CR+PR) was 18/38 (47.4%), and CR+PR+SD rate was 31/38 (81.6%). Grade 3/4 adverse effect included leukopenia (50.0%), neutropenia (52.6%), anemia (18.4%) and thrombocytopenia (2.6%), nausea/vomiting (7.9%) and diarrhea (2.6%). Treatment-related death was not observed. Median PFS was 7 months (range 1–33) and OS was 19 months (range 4–60). Among 20 pts with platinum resistant cases, RR was 6/20 (30.0%), CR+PR+SD rate was 14/20 (70.0%), median PFS was 6 months (range 1–33), and OS was 24 months (range 5–60). Conclusions: Combination irinotecan/oral etoposide chemotherapy can achieve a superior management for the recurrent ovarian cancer without declining QOL, and also has the possibility to be one of the most effective regimens as second-line chemotherapy. No significant financial relationships to disclose.

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