scholarly journals Guardant360 Circulating Tumor DNA Assay Is Concordant with FoundationOne Next‐Generation Sequencing in Detecting Actionable Driver Mutations in Anti‐EGFR Naive Metastatic Colorectal Cancer

2019 ◽  
Vol 25 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Rohan Gupta ◽  
Tamer Othman ◽  
Chen Chen ◽  
Jaideep Sandhu ◽  
Ching Ouyang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Metastatic Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Driver Mutations ◽  
Next Generation ◽  
Dna Assay ◽  
Tumor Dna ◽  
Generation Sequencing

Next Generation Sequencing of Circulating Tumor DNA Can Optimize Second Line Treatment in RAS Wild Type Metastatic Colorectal Cancer after Progression on Anti-EGFR Therapy: Time to Rethink Our Approach

2022 ◽  
Author(s):  
Davide Mauri ◽  
Konstantinos Kamposioras ◽  
Dimitris Matthaios ◽  
Maria Tolia ◽  
Ioanna Nixon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Metastatic Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Clinical Approach ◽  
Line Treatment ◽  
Next Generation ◽  
Wild Type ◽  
Tumor Dna ◽  
Generation Sequencing

Background Management of Raswild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. Development of treatment resistance with prevalence of pre-existing RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. Summary The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation Next Generation Sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify drugable mutations or recovery of RAS-wildness. In this opinion paper we summarize with critical thinking the clinical approach to be followed after the failure of first line treatment in Ras wild-type CRC tumors with the use of NGS. Key Messages Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of Ras wildness, and targeted approach of specific mutations (BRAF inhibitors) amplifications (anti-Her2 treatment) or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic colorectal cancer and guide clinical decisions. NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

scholarly journals Postoperative Circulating Tumor DNA Can Predict High Risk Patients with Colorectal Cancer Based on Next-Generation Sequencing

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4190
Author(s):  
Chul-Seung Lee ◽  
Hoon-Seok Kim ◽  
Jeoffrey Schageman ◽  
In-Kyu Lee ◽  
Myungshin Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Treatment Strategies ◽  
Circulating Tumor Dna ◽  
R0 Resection ◽  
Next Generation ◽  
Post Operation ◽  
Ctdna Analysis ◽  
Tumor Dna ◽  
Generation Sequencing

The objective of this study was to characterize circulating tumor DNA (ctDNA) mutations in colorectal cancer (CRC) patients and evaluate their prognostic values during treatment. Forty-nine patients with CRC planned for operation were enrolled. A total of 115 plasma samples were collected pre-operation, post-operation, and post-chemotherapy. ctDNA analysis was performed using next-generation sequencing (NGS) including 14 genes. In 22 (44.9%) out of 49 patients, at least one mutation (40 total mutations) was detected in the initial plasma sample. The median sum of variant allele frequency was 0.74% (range: 0.10–29.57%). TP53 mutations were the most frequent (17 of 49 patients, 34.7%), followed by APC (18.4%), KRAS (12.2%), FBXW7 (8.2%), NRAS (2.0%), PIK3CA (2.0%), and SMAD4 (2.0%). After surgery, five (14.3%) out of 35 patients harbored ctDNA mutation. All five patients experienced relapse or metastasis during follow-up. It was noteworthy that all three patients with persistent ctDNA relapsed after R0 resection. After chemotherapy, ctDNA analysis was performed for 31 patients, all of which were ctDNA-negative. Analytical and clinical performances of NGS to utilize ctDNA in CRC were determined. Results revealed that postoperative ctDNA might serve as a marker for identifying risk of recurrence, thus contributing to patient-oriented treatment strategies.

scholarly journals Carrier molecules and extraction of circulating tumor DNA for next generation sequencing in colorectal cancer

2016 ◽  
Vol 59 (2) ◽  
pp. 54-58 ◽  
Author(s):  
Martin Beránek ◽  
Igor Sirák ◽  
Milan Vošmik ◽  
Jiří Petera ◽  
Monika Drastíková ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Somatic Mutations ◽  
Circulating Tumor Dna ◽  
Next Generation ◽  
Sequencing Data ◽  
Polyadenylic Acid ◽  
Sperm Dna ◽  
Tumor Dna ◽  
Generation Sequencing

The aims of the study were:i) to compare circulating tumor DNA (ctDNA) yields obtained by different manual extraction procedures,ii) to evaluate the addition of various carrier molecules into the plasma to improve ctDNA extraction recovery, andiii) to use next generation sequencing (NGS) technology to analyzeKRAS,BRAF, andNRASsomatic mutations in ctDNA from patients with metastatic colorectal cancer. Venous blood was obtained from patients who suffered from metastatic colorectal carcinoma. For plasma ctDNA extraction, the following carriers were tested: carrier RNA, polyadenylic acid, glycogen, linear acrylamide, yeast tRNA, salmon sperm DNA, and herring sperm DNA. Each extract was characterized by quantitative real-time PCR and next generation sequencing. The addition of polyadenylic acid had a significant positive effect on the amount of ctDNA eluted. The sequencing data revealed five cases of ctDNA mutated inKRASand one patient with aBRAFmutation. An agreement of 86% was found between tumor tissues and ctDNA. Testing somatic mutations in ctDNA seems to be a promising tool to monitor dynamically changing genotypes of tumor cells circulating in the body. The optimized process of ctDNA extraction should help to obtain more reliable sequencing data in patients with metastatic colorectal cancer.

scholarly journals Next-Generation Sequencing-Based Monitoring of Circulating Tumor DNA Reveals Clonotypic Heterogeneity in Untreated PTCL

2021 ◽  
Author(s):  
Milos D Miljkovic ◽  
Christopher Melani ◽  
Stefania Pittaluga ◽  
Rahul Lakhotia ◽  
Andrea Nicole Lucas ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
T Cell ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Driver Mutations ◽  
Next Generation ◽  
Serum Samples ◽  
Baseline Serum ◽  
Tumor Dna ◽  
Generation Sequencing

Peripheral T-cell lymphomas (PTCL) have marked biologic and clinical heterogeneity, which confounds treatment decisions. Advances in circulating tumor DNA (ctDNA) assays employing next generation sequencing (NGS) has improved the detection of molecular relapse and driver mutations in diffuse large B-cell lymphoma, and highlight the potential utility of ctDNA across lymphomas. We investigated NGS-based monitoring of T-cell receptor (TCR) sequences in PTCL patients undergoing frontline treatment (NCT00001337). Of 45 patients, 34 (76%) had tumor-specific clonotypes of the TCR β or ɣ genes identified, which included 18 (86%) from baseline tissue and 16 (67%) from baseline serum. Twenty-five (74%) patients had both TCRβ and TCRɣ clonotypes, 23 (68%) patients had more than one TCRɣ clonotype, and 4 (9%) had multiple TCRβ or TCRɣ clonotypes, demonstrating significant intra-patient clonotypic heterogeneity. Among 24 patients with available serial serum samples during treatment, 9 (38%) cleared ctDNA after 2 cycles of therapy, and 11 (46%) patients had detectable ctDNA at the end of treatment. Patients with detectable ctDNA after therapy showed a trend towards worse survival. Notably, two patients with persistently detectable ctDNA after therapy remain in remission with 10-years of follow-up. Clonotypic heterogeneity in tumors and persistence despite long-term remission suggests variability in oncological potential.

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