scholarly journals NGS Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Melanoma Samples Using Oncomine™ Pan-Cancer Cell-Free Assay

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1080
Author(s):  
Magdalena Olbryt ◽  
Marcin Rajczykowski ◽  
Wiesław Bal ◽  
Anna Fiszer-Kierzkowska ◽  
Alexander Jorge Cortez ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Liquid Biopsy ◽  
High Sensitivity ◽  
Genetic Profile ◽  
Liquid Biopsies ◽  
Braf Mutations ◽  
Genetic Profiling ◽  
Pathogenic Variants ◽  
Ffpe Tumor ◽  
Pan Cancer

Next-generation sequencing (NGS) in liquid biopsies may contribute to the diagnosis, monitoring, and personalized therapy of cancer through the real-time detection of a tumor’s genetic profile. There are a few NGS platforms offering high-sensitivity sequencing of cell-free DNA (cfDNA) samples. The aim of this study was to evaluate the Ion AmpliSeq HD Technology for targeted sequencing of tumor and liquid biopsy samples from patients with fourth-stage melanoma. Sequencing of 30 samples (FFPE tumor and liquid biopsy) derived from 14 patients using the Oncomine™ Pan-Cancer Cell-Free Assay was performed. The analysis revealed high concordance between the qPCR and NGS results of the BRAF mutation in FFPE samples (91%), as well as between the FFPE and liquid biopsy samples (91%). The plasma-tumor concordance of the non-BRAF mutations was 28%. A total of 17 pathogenic variants in 14 genes (from 52-gene panel), including TP53, CTNNB1, CCND1, MET, MAP2K1, and GNAS, were identified, with the CTNNB1S45F variant being the most frequent. A positive correlation between the LDH level and cfDNA concentration as well as negative correlation between the LDH level and time to progression was confirmed in a 22-patient cohort. The analysis showed both the potential and limitations of liquid biopsy genetic profiling using HD technology and the Ion Torrent platform.

scholarly journals Identification of Tumor Specific Neoantigens and Their Implications in Dendritic Cell Immunotherapy Using Liquid Biopsy Results: Findings from an Observational Cohort Study

2021 ◽  
Author(s):  
Khin Zay Yar Myint ◽  
Masamori Shimabuku ◽  
Ruriko Horio ◽  
Munehisa Kaneda ◽  
Yoko Shimizu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Specific Antigen ◽  
Cost Effective ◽  
Average Frequency ◽  
Liquid Biopsies ◽  
Genetic Profiling ◽  
Cell Immunotherapy ◽  
Tumor Biopsies

Abstract Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using these antigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for tumor-specific antigen-based immunotherapy and the importance of tailoring immunotherapy in accordance with the liquid biopsy result in each treatment stage.

scholarly journals Identification of Tumor Specific Neoantigens and Their Implications in Dendritic Cell Immunotherapy Using Liquid Biopsy Results: Findings from an Observational Cohort Study

2021 ◽  
Author(s):  
Khin Zay Yar Myint ◽  
Masanari Shimabuku ◽  
Ruriko Horio ◽  
Munehisa Kaneda ◽  
Yoko Shimizu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Cost Effective ◽  
Average Frequency ◽  
Liquid Biopsies ◽  
Genetic Profiling ◽  
Cell Immunotherapy ◽  
Observational Cohort ◽  
Tumor Biopsies

Abstract Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using neoantigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for neoantigen-based immunotherapy and the importance of tailoring neoantigen-based immunotherapy in accordance with the liquid biopsy result in each treatment stage.

scholarly journals Identification of Tumor Specific Neoantigens and Their Implications in Dendritic Cell Immunotherapy Using Liquid Biopsy Results: Findings from an Observational Cohort Study

2021 ◽  
Author(s):  
Khin Zay Yar Myint ◽  
Masamori Shimabuku ◽  
Ruriko Horio ◽  
Munehisa Kaneda ◽  
Yoko Shimizu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Liquid Biopsy ◽  
Clonal Evolution ◽  
Cost Effective ◽  
Average Frequency ◽  
Liquid Biopsies ◽  
Genetic Profiling ◽  
Cell Immunotherapy ◽  
Observational Cohort ◽  
Tumor Biopsies

Abstract Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using neoantigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for neoantigen-based immunotherapy and the importance of tailoring neoantigen-based immunotherapy in accordance with the liquid biopsy result in each treatment stage.

Abstract A03: Evaluation of the Oncomine Pan-Cancer Cell-Free Assay for liquid biopsy profiling

2020 ◽  
Author(s):  
Jane Bayani ◽  
Megan Hopkins ◽  
Melanie Spears ◽  
John M. S. Bartlett
Keyword(s):  
Cancer Cell ◽  
Liquid Biopsy ◽  
Pan Cancer

Liquid biopsy for BRAF mutations testing in non-small cell lung cancer: a retrospective study

2020 ◽  
pp. jclinpath-2020-207107
Author(s):  
Antonino Iaccarino ◽  
Pasquale Pisapia ◽  
Francesco Pepe ◽  
Roberta Sgariglia ◽  
Mariantonia Nacchio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Liquid Biopsies ◽  
Braf Mutations ◽  
Advanced Stages ◽  
Nsclc Patients

V-Raf murine sarcoma viral oncogene homolog B (BRAF) gene mutations have recently been approved to select advanced stages non-small cell lung cancer (NSCLC) patients for tyrosine kinase inhibitors treatments. In this setting, liquid biopsy may represent a valuable option for BRAF mutational testing in patients without tissue availability. Here, we reviewed 196 plasma based liquid biopsies analysed by an in-house developed next generation sequencing panel, termed SiRe. On the overall, 6 (3.1%) out of 196 BRAF mutated cases were identified, with an overall median allelic frequency of 3.4%. Exon 15 p.V600E was the most common detected mutation (2/6, 33.3%). Our data highlighted that the SiRe panel is a robust tool for BRAF mutation assessment on circulating tumour DNA. Further investigation is required to develop a diagnostic algorithm to harmonise BRAF testing on tissue and blood in advanced stages NSCLC patients.

scholarly journals Clinical Utility of Liquid Biopsy-Based Actionable Mutations Detected via ddPCR

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 906
Author(s):  
Irina Palacín-Aliana ◽  
Noemí García-Romero ◽  
Adrià Asensi-Puig ◽  
Josefa Carrión-Navarro ◽  
Víctor González-Rumayor ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
Cancer Genetics ◽  
High Sensitivity ◽  
Digital Pcr ◽  
Liquid Biopsies ◽  
Cancer Subtypes ◽  
Cancer Management ◽  
Main Challenge ◽  
Therapeutic Decisions

Cancer is one of the leading causes of death worldwide and remains a major public health challenge. The introduction of more sensitive and powerful technologies has permitted the appearance of new tumor-specific molecular aberrations with a significant cancer management improvement. Therefore, molecular pathology profiling has become fundamental not only to guide tumor diagnosis and prognosis but also to assist with therapeutic decisions in daily practice. Although tumor biopsies continue to be mandatory in cancer diagnosis and classification, several studies have demonstrated that liquid biopsies could be used as a potential tool for the detection of cancer-specific biomarkers. One of the main advantages is that circulating free DNA (cfDNA) provides information about intra-tumoral heterogeneity, reflecting dynamic changes in tumor burden. This minimally invasive tool has become an accurate and reliable instrument for monitoring cancer genetics. However, implementing liquid biopsies across the clinical practice is still ongoing. The main challenge is to detect genomic alterations at low allele fractions. Droplet digital PCR (ddPCR) is a powerful approach that can overcome this issue due to its high sensitivity and specificity. Here we explore the real-world clinical utility of the liquid biopsy ddPCR assays in the most diagnosed cancer subtypes.

scholarly journals Limited Practical Utility of Liquid Biopsy in the Treated Patients with Advanced Breast Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 523
Author(s):  
Anna Niwinska ◽  
Aneta Bałabas ◽  
Maria Kulecka ◽  
Anna Kluska ◽  
Magdalena Piątkowska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liquid Biopsy ◽  
Clinical Utility ◽  
Stage Iv ◽  
Copy Number Variations ◽  
Stage Iii ◽  
Cancer Genes ◽  
Pathogenic Variants ◽  
Hotspot Mutations ◽  
Pan Cancer

Recently, liquid biopsy has emerged as a tool to monitor oncologic disease progression and the effects of treatment. In this study we aimed to determine the clinical utility of liquid biopsy relative to conventional oncological post-treatment surveillance. Plasma cell-free (cf) DNA was collected from six healthy women and 37 patients with breast cancer (18 and 19 with stage III and IV tumors, respectively). CfDNA was assessed using the Oncomine Pan-Cancer Cell-Free Assay. In cfDNA samples from patients with BC, 1112 variants were identified, with only a few recurrent or hotspot mutations within specific regions of cancer genes. Of 65 potentially pathogenic variants detected in tumors, only 19 were also discovered in at least one blood sample. The allele frequencies of detected variants (VAFs) were <1% in cfDNA from all controls and patients with stage III BC, and 24/85 (28.2%) variants had VAFs > 1% in only 8 of 25 (32%) patients with stage IV BC. Copy number variations (CNVs) spanning CDK4, MET, FGFR1, FGFR2, ERBB2, MYC, and CCND3 were found in 1 of 12 (8%) and 8 of 25 (32%) patients with stage III and IV tumors, respectively. In healthy controls and patients without BC progression after treatment, VAFs were <1%, while in patients with metastatic disease and/or more advanced genomic alterations, VAFs > 1% and/or CNV were detected in approximately 30%. Therefore, most patients with stage IV BC could not be distinguished from those with stage III disease following therapy, based on liquid biopsy results.

A Novel Method for Microsatellite Instability Detection by Liquid Biopsy Based on Next- Generation Sequencing

2020 ◽  
Vol 15 ◽  
Author(s):  
Zheng Jiang ◽  
Hui Liu ◽  
Siwen Zhang ◽  
Jia Liu ◽  
Weitao Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Microsatellite Instability ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
High Sensitivity ◽  
Next Generation ◽  
Tissue Samples ◽  
Next Generation Sequencing Technology ◽  
Medication Selection ◽  
Generation Sequencing

Background: Microsatellite instability (MSI) is a prognostic biomarker used to guide medication selection in multiple cancers, such as colorectal cancer. Traditional PCR with capillary electrophoresis and next-generation sequencing using paired tumor tissue and leukocyte samples are the main approaches for MSI detection due to their high sensitivity and specificity. Currently, patient tissue samples are obtained through puncture or surgery, which causes injury and risk of concurrent disease, further illustrating the need for MSI detection by liquid biopsy. Methods: We propose an analytic method using paired plasma/leukocyte samples and MSI detection using next-generation sequencing technology. Based on the theoretical progress of oncogenesis, we hypothesized that the microsatellite site length in plasma equals the combination of the distribution of tumor tissue and leukocytes. Thus, we defined a window-judgement method to identify whether biomarkers were stable. Results: Compared to traditional PCR as the standard, we evaluated three methods in 20 samples (MSI-H:3/MSS:17): peak shifting method using tissue vs. leukocytes, peak shifting method using plasma vs. leukocytes, and our method using plasma vs. leukocytes. Compared to traditional PCR, we observed a sensitivity of 100%, 0%, and 100%, and a specificity of 100.00%, 94.12%, and 88.24%, respectively. Conclusion: Our method has the advantage of possibly detecting MSI in a liquid biopsy and provides a novel direction for future studies to increase the specificity of the method.

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