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.

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.

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.

Next-generation sequencing-based BRCA testing on cytological specimens from ovarian cancer ascites reveals high concordance with tumour tissue analysis

2019 ◽  
Vol 73 (3) ◽  
pp. 168-171 ◽  
Author(s):  
Caterina Fumagalli ◽  
Alessandra Rappa ◽  
Chiara Casadio ◽  
Ilaria Betella ◽  
Nicoletta Colombo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Clinical Decision Making ◽  
Parp Inhibitor ◽  
Clinical Decision ◽  
Tumour Tissue ◽  
Next Generation ◽  
High Concordance ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

BackgroundWith the approval of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for newly diagnosed, breast cancer gene (BRCA)1/2 mutated, ovarian cancer women, the assessment of BRCA1/2 tumour status will be shortly required at the time of diagnosis.AimTo investigate the feasibility of next-generation sequencing (NGS)-based BRCA tumour test on cytological specimens from ovarian cancer ascites.MethodsWe evaluated the BRCA1/2 status on neoplastic ascites and corresponding tumour tissue of 11 patients with ovarian cancer, using the NGS ‘Oncomine BRCA Research Assay’.ResultsThe NGS-based BRCA test on cytological samples had a success rate of 100%, with 11 of 11 concordant BRCA1/2 results between ascites and tumour tissues analyses, including two wild type samples and nine cases harbouring somatic or germline variants.ConclusionBRCA test may be performed on ovarian cancer ascites, reproducing BRCA1/2 tumour status and representing a useful tool for clinical decision-making.

scholarly journals Assuring the Quality of Next-Generation Sequencing in Clinical Microbiology and Public Health Laboratories

2016 ◽  
Vol 54 (12) ◽  
pp. 2857-2865 ◽  
Author(s):  
Amy S. Gargis ◽  
Lisa Kalman ◽  
Ira M. Lubin
Keyword(s):  
Public Health ◽  
Next Generation Sequencing ◽  
Clinical Microbiology ◽  
Next Generation ◽  
Standards And Guidelines ◽  
Control Procedures ◽  
Next Generation Sequencing Ngs ◽  
Professional Guidelines ◽  
Generation Sequencing

Clinical microbiology and public health laboratories are beginning to utilize next-generation sequencing (NGS) for a range of applications. This technology has the potential to transform the field by providing approaches that will complement, or even replace, many conventional laboratory tests. While the benefits of NGS are significant, the complexities of these assays require an evolving set of standards to ensure testing quality. Regulatory and accreditation requirements, professional guidelines, and best practices that help ensure the quality of NGS-based tests are emerging. This review highlights currently available standards and guidelines for the implementation of NGS in the clinical and public health laboratory setting, and it includes considerations for NGS test validation, quality control procedures, proficiency testing, and reference materials.

Reliability and reproducibility among different platforms for tumour BRCA testing in ovarian cancer: a study of the Italian NGS Network

2020 ◽  
pp. jclinpath-2020-206800
Author(s):  
Caterina Fumagalli ◽  
Elena Guerini-Rocco ◽  
Fiamma Buttitta ◽  
Pierluigi Iapicca ◽  
Wenqi You ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Variant Calling ◽  
Diagnostic Procedures ◽  
Quality Parameters ◽  
Third Party ◽  
Raw Data ◽  
Bioinformatic Pipeline ◽  
Pathogenic Variants ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

IntroductionBRCA tumour testing is a crucial tool for personalised therapy of patients with ovarian cancer. Since different next-generation sequencing (NGS) platforms and BRCA panels are available, the NGS Italian Network proposed to assess the robustness of different technologies.MethodsSix centres, using four different technologies, provided raw data of 284 cases, including 75 cases with pathogenic/likely pathogenic variants, for a revision blindly performed by an external bioinformatic platform.ResultsThe third-party revision assessed that all the 284 raw data reached good quality parameters. The variant calling analysis confirmed all the 75 pathogenic/likely pathogenic variants, including challenging variants, achieving a concordance rate of 100% regardless of the panel, instrument and bioinformatic pipeline adopted. No additional variants were identified in the reanalysis of a subset of 41 cases.ConclusionsBRCA tumour testing performed with different technologies in different centres, may achieve the realibility and reproducibility required for clinical diagnostic procedures.

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.

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