RNAseq in addition to next generation sequencing in advanced genitourinary cancers reveals transcriptomic silencing of DNA mutations: Implications for resistance to targeted therapeutics.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 583-583 ◽  
Author(s):  
Jacob J. Adashek ◽  
Shumei Kato ◽  
Rahul Parulkar ◽  
Christopher Szeto ◽  
Sandeep K. Reddy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bladder Cancer ◽  
Next Generation Sequencing ◽  
Kidney Cancer ◽  
Next Generation ◽  
Dna And Rna ◽  
Number Of Patients ◽  
Study Results ◽  
Dna Alterations ◽  
Generation Sequencing

583 Background: Next generation sequencing (NGS) for advanced tumors is becoming more routine. However, not all patients respond to precision matched treatments. We hypothesized that one potential reason for treatment failure with targeted therapy could be discrepancies between DNA alterations and RNA expression. Methods: Tumor samples from patients with metastatic kidney, bladder, and prostate cancer were analyzed by whole exome or whole genome NGS and RNA sequencing (CLIA-certified laboratory; NantOmics LLC, Santa Cruz, CA). Only known pathogenic driver alterations were analyzed in the current study. Results: Of 45 patients, 10 had kidney cancer, 18 had bladder cancer; and 17 had prostate cancer. Median age was 66 years (range, 28 - 86). The most commonly altered genes were TP53 (35.6% [16/45]), PIK3CA (15.6% [7/45]), FGFR3 (11.1% [5/45]), ALK (8.9% [4/45]), and ATM (8.9% [4/45]). In total, 86 pathogenic DNA alterations were identified; 17 of these (19.8%) were not observed at the RNA level. Among 45 patients, 31.1% (14/45) had ≥1 DNA alteration that was not expressed at the RNA level. Discordance between DNA and RNA was seen in 40% of patients with kidney cancer (4/10), 28% of patients with bladder cancer (5/18), and 29% with prostate cancer (5/17). Examples of genes that had pathogenic DNA alterations not seen at the RNA level included ALK (four discordant cases), KDR (three discordant cases) and GNAS (one discordant case). On the other hand, alterations involving certain genes showed 100% concordance between DNA and RNA: TP53 [N = 16], PIK3CA [N = 7], and FGFR3 [N = 5]). Conclusions: A significant number of patients with genitourinary tumors had DNA alterations that are silenced at the RNA level (19.8%). Transcriptomic silencing merits additional investigation as a mechanism that could mediate resistance to therapeutics targeted at cognate alterations.

scholarly journals Datasets for next-generation sequencing of DNA and RNA from urine and plasma of patients with prostate cancer

Data in Brief ◽  
2017 ◽  
Vol 10 ◽  
pp. 369-372 ◽  
Author(s):  
A.S. Nikitina ◽  
E.I. Sharova ◽  
S.A. Danilenko ◽  
O.V. Selezneva ◽  
T.B. Butusova ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Dna And Rna ◽  
Generation Sequencing

Next generation sequencing panels to predict response to hormonal therapy in prostate cancer

2016 ◽  
Author(s):  
Heini M L Kallio ◽  
Matti Annala ◽  
Anniina Brofeldt ◽  
Reija Hieta ◽  
Kati Kivinummi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
Hormonal Therapy ◽  
Next Generation ◽  
Generation Sequencing

The applications of next-generation sequencing (NGS) in drug development for cancer therapy

2020 ◽  
Vol 16 ◽  
Author(s):  
Pelin Telkoparan-Akillilar ◽  
Dilek Cevik
Keyword(s):  
Next Generation Sequencing ◽  
Drug Discovery ◽  
Cancer Therapy ◽  
Target Identification ◽  
Rapid Development ◽  
Next Generation ◽  
Biomedical Sciences ◽  
Dna And Rna ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Background: Numerous sequencing techniques have been progressed since the 1960s with the rapid development of molecular biology studies focusing on DNA and RNA. Methods: a great number of articles, book chapters, websites are reviewed, and the studies covering NGS history, technology and applications to cancer therapy are included in the present article. Results: High throughput next-generation sequencing (NGS) technologies offer many advantages over classical Sanger sequencing with decreasing cost per base and increasing sequencing efficiency. NGS technologies are combined with bioinformatics software to sequence genomes to be used in diagnostics, transcriptomics, epidemiologic and clinical trials in biomedical sciences. The NGS technology has also been successfully used in drug discovery for the treatment of different cancer types. Conclusion: This review focuses on current and potential applications of NGS in various stages of drug discovery process, from target identification through to personalized medicine.

scholarly journals Development and Optimization of Metagenomic Next-Generation Sequencing Methods for Cerebrospinal Fluid Diagnostics

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Patricia J. Simner ◽  
Heather B. Miller ◽  
Florian P. Breitwieser ◽  
Gabriel Pinilla Monsalve ◽  
Carlos A. Pardo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Next Generation Sequencing ◽  
Sample Pretreatment ◽  
Standard Of Care ◽  
Nucleic Acid Amplification ◽  
Next Generation ◽  
Bead Beating ◽  
Dna And Rna ◽  
Positive Threshold ◽  
Generation Sequencing

ABSTRACT The purpose of this study was to develop and optimize different processing, extraction, amplification, and sequencing methods for metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) specimens. We applied mNGS to 10 CSF samples with known standard-of-care testing (SoC) results (8 positive and 2 negative). Each sample was subjected to nine different methods by varying the sample processing protocols (supernatant, pellet, neat CSF), sample pretreatment (with or without bead beating), and the requirement of nucleic acid amplification steps using DNA sequencing (DNASeq) (with or without whole-genome amplification [WGA]) and RNA sequencing (RNASeq) methods. Negative extraction controls (NECs) were used for each method variation (4/CSF sample). Host depletion (HD) was performed on a subset of samples. We correctly determined the pathogen in 7 of 8 positive samples by mNGS compared to SoC. The two negative samples were correctly interpreted as negative. The processing protocol applied to neat CSF specimens was found to be the most successful technique for all pathogen types. While bead beating introduced bias, we found it increased the detection yield of certain organism groups. WGA prior to DNASeq was beneficial for defining pathogens at the positive threshold, and a combined DNA and RNA approach yielded results with a higher confidence when detected by both methods. HD was required for detection of a low-level-positive enterovirus sample. We demonstrate that NECs are required for interpretation of these complex results and that it is important to understand the common contaminants introduced during mNGS. Optimizing mNGS requires the use of a combination of techniques to achieve the most sensitive, agnostic approach that nonetheless may be less sensitive than SoC tools.

scholarly journals Transcriptomics Signature from Next-Generation Sequencing Data Reveals New Transcriptomic Biomarkers Related to Prostate Cancer

2019 ◽  
Vol 18 ◽  
pp. 117693511983552 ◽  
Author(s):  
Abedalrhman Alkhateeb ◽  
Iman Rezaeian ◽  
Siva Singireddy ◽  
Dora Cavallo-Medved ◽  
Lisa A Porter ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
Cancer Progression ◽  
Machine Learning Techniques ◽  
Next Generation Sequencing Data ◽  
Prognostic Indicators ◽  
Next Generation ◽  
Sequencing Data ◽  
Cancer Data ◽  
Generation Sequencing

Prostate cancer is one of the most common types of cancer among Canadian men. Next-generation sequencing using RNA-Seq provides large amounts of data that may reveal novel and informative biomarkers. We introduce a method that uses machine learning techniques to identify transcripts that correlate with prostate cancer development and progression. We have isolated transcripts that have the potential to serve as prognostic indicators and may have tremendous value in guiding treatment decisions. Analysis of normal versus malignant prostate cancer data sets indicates differential expression of the genes HEATR5B, DDC, and GABPB1-AS1 as potential prostate cancer biomarkers. Our study also supports PTGFR, NREP, SCARNA22, DOCK9, FLVCR2, IK2F3, USP13, and CLASP1 as potential biomarkers to predict prostate cancer progression, especially between stage II and subsequent stages of the disease.

Next-generation sequencing reveals novel rare fusion events with functional implication in prostate cancer

Oncogene ◽  
2014 ◽  
Vol 34 (5) ◽  
pp. 568-577 ◽  
Author(s):  
I Teles Alves ◽  
T Hartjes ◽  
E McClellan ◽  
S Hiltemann ◽  
R Böttcher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Functional Implication ◽  
Generation Sequencing

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
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