scholarly journals Gene Copy Number Estimation from Targeted Next-Generation Sequencing of Prostate Cancer Biopsies: Analytic Validation and Clinical Qualification

2017 ◽  
Vol 23 (20) ◽  
pp. 6070-6077 ◽  
Author(s):  
George Seed ◽  
Wei Yuan ◽  
Joaquin Mateo ◽  
Suzanne Carreira ◽  
Claudia Bertan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Next Generation ◽  
Copy Number Estimation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Targeted Amplicon Based Next-Generation Sequencing Facilitates Detection of KMT2A/MLL Gene Copy Number Changes

2017 ◽  
Vol 214-215 ◽  
pp. 41-42
Author(s):  
Rashmi Kanagal-Shamanna ◽  
Xinyan Lu ◽  
Wei Chen ◽  
Mark Routbort ◽  
Bedia Barkoh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Next Generation ◽  
Mll Gene ◽  
Copy Number Changes ◽  
Generation Sequencing

scholarly journals MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lun-Xi Peng ◽  
Guang-Ling Jie ◽  
An-Na Li ◽  
Si-Yang Liu ◽  
Hao Sun ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Copy Number ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Precision Oncology ◽  
Next Generation ◽  
Driver Genes ◽  
Generation Sequencing

Abstract Background MET amplification plays an important role in the development of non-small-cell lung cancer (NSCLC) either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Fluorescence in situ hybridization (FISH) is the standard method for MET amplification. With more and more discoveries of oncogenic driver genes, next-generation sequencing (NGS) plays a significant role in precision oncology. Meanwhile, the role of NGS in MET amplification remains uncertain. Methods Forty patients diagnosed with advanced NSCLC were included. FISH and NGS were conducted prior to MET inhibitors treatment. MET amplification by FISH was defined as a MET/CEP7 ratio of  >  2.0 and/or copy number (CN)  >  5. MET amplification by NGS was defined as gene copy number (GCN)  ≥  5. Results The concordance rate among FISH and NGS was 62.5% (25/40). MET amplification identified by FISH showed the optimal predictive value. The partial response (PR) rate was 68.0% (17/25 with MET amplification) vs. 6.7% (1/15 without MET amplification); the median progression-free survival (PFS) was 5.4 months versus 1.0 months (P  < 0.001). MET amplification identified by NGS failed to distinguish significant clinical outcomes. The PR rate was 60.0% (6/10, with MET GCN  ≥ 5) vs. 40.0% (12/30, with MET GCN  < 5); the median PFS was 4.8 months vs. 2.2 months (P  = 0.357). The PR rate was 68.8% (11/16) and the median PFS was 4.8 months in patients with focal amplification by NGS. Conclusions MET amplification identified by FISH remains the optimal biomarker to identify suitable candidates for MET-TKI therapy. In comparison, amplification identified by NGS seems not as robust to be effective predictive biomarker. Further exploration is needed regarding the focal amplification by NGS in predicting the efficacy.

scholarly journals Next generation sequencing is a highly reliable method to analyze exon 7 deletion of survival motor neuron 1 (SMN1) gene

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Sumin Zhao ◽  
Yaoshen Wang ◽  
Xiuqing Xin ◽  
Zhonghai Fang ◽  
Linlin Fan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Copy Number ◽  
Reliable Method ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Copy Number ◽  
Carrier Screening ◽  
Gene Copy ◽  
Next Generation ◽  
Expanded Carrier Screening ◽  
Generation Sequencing

AbstractSpinal muscular atrophy (SMA) is one of the most common and severe genetic diseases. SMA carrier screening is an effective way to identify couples at risk of having affected children. Next-generation sequencing (NGS)-based expanded carrier screening could detect SMN1 gene copy number without extra experiment and with high cost performance. However, its performance has not been fully evaluated. Here we conducted a systematic comparative study to evaluate the performance of three common methods. 478 samples were analyzed with multiplex ligation probe amplification (MLPA), real-time quantitative polymerase chain reaction (qPCR) and NGS, simultaneously. Taking MLPA-based results as the reference, for 0 copy, 1 copy and ≥ 2 copy SMN1 analysis with NGS, the sensitivity, specificity and precision were all 100%. Using qPCR method, the sensitivity was 100%, 97.52% and 94.30%, respectively; 98.63%, 95.48% and 100% for specificity; and 72.72%, 88.72% and 100% for precision. NGS repeatability was higher than that of qPCR. Moreover, among three methods, NGS had the lowest retest rate. Thus, NGS is a relatively more reliable method for SMN1 gene copy number detection. In expanded carrier screening, compared with the combination of multiple methods, NGS method could reduce the test cost and simplify the screening process.

Targeted Next-Generation Sequencing in Men with Metastatic Prostate Cancer: a Pilot Study

2018 ◽  
Vol 13 (4) ◽  
pp. 495-500 ◽  
Author(s):  
Pedro C. Barata ◽  
Prateek Mendiratta ◽  
Brandie Heald ◽  
Stefan Klek ◽  
Petros Grivas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
Pilot Study ◽  
Metastatic Prostate Cancer ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Next generation sequencing of primary prostate cancer tumors to reveal potentially actionable opportunities for clinical management: The UNC experience.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 305-305
Author(s):  
Daniel James Crona ◽  
Anthony Drier ◽  
Jing Daisy Zhu ◽  
Emily Fox Bell ◽  
Margaret Rose Sketch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
Copy Number Variations ◽  
Precision Oncology ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Formalin Fixed Paraffin ◽  
Primary Prostate Cancer ◽  
Formalin Fixed Paraffin Embedded ◽  
Generation Sequencing

305 Background: The Strata trial (NCT03061305) is a multi-institutional precision oncology collaboration structured as an observational protocol that aims to match patients to genomically-guided therapies. Methods: Selected University of North Carolina (UNC) metastatic prostate cancer (mPC) patients were enrolled on this IRB-approved study. Formalin fixed paraffin-embedded primary tumor specimens, without matched germline controls, were sent for targeted next generation sequencing (NGS) to detect actionable variants, including: mutations in 87 genes, copy number variations in 31 genes, and gene fusions in 46 gene drivers. mPC-related genes of particular interest included: AR, ATM, BRCA1/2, ERG, MSH2, MSH6, PTEN, RB1, and TP53. Results: Of the 92 cases sequenced, 5 [5%] failed testing. Of the 87 mPC patients (median age 69 years [47-86]) enrolled: 53 [61%] were white, 28 [32%] were black, 1 [1%] was Asian, and 5 [6%] declined to be identified. NGS data revealed 106 variants in 27 genes: 62 patients (71%) had at least one variant, 21 (24%) had 2 variants, 7 (8%) had 3 variants, and 4 (3%) had 4 variants. Among the 62 patients with at least 1 identified variant, TMPRSS2-ERG fusion occurred most frequently (50%), followed by TP53 (40%), and PTEN (16%). 6% of all sequenced patients had variants in DNA damage repair genes including ATM (3%), BRCA2 (2%) and MSH2 (1%). One patient had a SLC45A3-ERG fusion combined with PTEN deep deletion, which has been associated with a more aggressive phenotype. One patient with a microsatellite-instability high tumor was treated with pembrolizumab. Conclusions: The UNC experience shows that a high proportion of primary prostate cancer tumors from mPC patients have genomic variants, and one patient was treated based on these data. Limited actionability may reflect the landscape of currently FDA approved mPC treatments, and available clinical trials. It may also be due to a short follow-up, and these data could inform treatment planning upon progression.

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