Liquid Biopsy: General Concepts

2019 ◽  
Vol 63 (6) ◽  
pp. 449-455 ◽  
Author(s):  
Geoffroy Poulet ◽  
Joséphine Massias ◽  
Valerie Taly
Keyword(s):  
Liquid Biopsy ◽  
Tumor Heterogeneity ◽  
Invasive Procedure ◽  
Digital Pcr ◽  
Cancer Tissue ◽  
Minimally Invasive Procedure ◽  
Cancer Evolution ◽  
Sequencing Technologies ◽  
Standardization Of Procedures ◽  
Generation Sequencing

Liquid biopsy provides the opportunity of detecting, analyzing and monitoring cancer in various body effluents such as blood or urine instead of a fragment of cancer tissue. It is composed of different biological matrices such as circulating tumor cells (CTCs), cell free nucleic acids, exosomes or tumors “educated platelets.” In addition to representing a non- or minimally invasive procedure, it should represent a better view of tumor heterogeneity and allows for real-time monitoring of cancer evolution. Recent technological and molecular advances, greatly facilitated by the use of microfluidics in many cases, have permitted large progresses both in our ability to purify and analyze liquid biopsy components. In particular, the great developments of droplet-based digital PCR and the various optimizations of next generation sequencing technologies are central to the several validations of CTC-free DNA as a strong cancer biomarker. However, complete adoption of liquid biopsy in clinics will require pursuing recent efforts in the standardization of procedures both on the pre-analytical and analytical aspects.

Measuring evolutionary cancer dynamics from genome sequencing, one patient at a time

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Giulio Caravagna
Keyword(s):  
Genome Sequencing ◽  
Cancer Evolution ◽  
Sequencing Data ◽  
Evolutionary Forces ◽  
Sequencing Technologies ◽  
Cancer Genome Sequencing ◽  
Multiple Resolutions ◽  
Multiple Patients ◽  
Single Tumour ◽  
Generation Sequencing

AbstractCancers progress through the accumulation of somatic mutations which accrue during tumour evolution, allowing some cells to proliferate in an uncontrolled fashion. This growth process is intimately related to latent evolutionary forces moulding the genetic and epigenetic composition of tumour subpopulations. Understanding cancer requires therefore the understanding of these selective pressures. The adoption of widespread next-generation sequencing technologies opens up for the possibility of measuring molecular profiles of cancers at multiple resolutions, across one or multiple patients. In this review we discuss how cancer genome sequencing data from a single tumour can be used to understand these evolutionary forces, overviewing mathematical models and inferential methods adopted in field of Cancer Evolution.

scholarly journals Epigenetic Biomarkers in Cell-Free DNA and Applications in Liquid Biopsy

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 32 ◽  
Author(s):  
Wanxia Gai ◽  
Kun Sun
Keyword(s):  
Cancer Diagnosis ◽  
Liquid Biopsy ◽  
Prenatal Testing ◽  
Digital Pcr ◽  
Liquid Biopsies ◽  
Sequencing Technologies ◽  
Epigenetic Biomarkers ◽  
Free Circulating Dna ◽  
Epigenetic Biomarker ◽  
Fragmentation Patterns

Cell-free circulating DNA (cfDNA) in plasma has gained global interest as a diagnostic material for noninvasive prenatal testing and cancer diagnosis, or the so-called “liquid biopsy”. Recent studies have discovered a great number of valuable genetic and epigenetic biomarkers for cfDNA-based liquid biopsy. Considering that the genetic biomarkers, e.g., somatic mutations, usually vary from case to case in most cancer patients, epigenetic biomarkers that are generalizable across various samples thus possess certain advantages. In this study, we reviewed the most recent studies and advances on utilizing epigenetic biomarkers for liquid biopsies. We first reviewed more traditional methods of using tissue/cancer-specific DNA methylation biomarkers and digital PCR or sequencing technologies for cancer diagnosis, as well as tumor origin determination. In the second part, we discussed the emerging novel approaches for exploring the biological basis and clinical applications of cfDNA fragmentation patterns. We further provided our comments and points of view on the future directions on epigenetic biomarker development for cfDNA-based liquid biopsies.

scholarly journals Deciphering Tumor Heterogeneity in Hepatocellular Carcinoma (HCC)—Multi-Omic and Singulomic Approaches

2021 ◽  
Author(s):  
Renumathy Dhanasekaran
Keyword(s):  
Single Cell ◽  
Tumor Heterogeneity ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Sampling Strategies ◽  
Cell Analysis ◽  
Single Cell Sequencing ◽  
Sequencing Technologies ◽  
Hepatocellular Carcinomas ◽  
Generation Sequencing

AbstractTumor heterogeneity, a key hallmark of hepatocellular carcinomas (HCCs), poses a significant challenge to developing effective therapies or predicting clinical outcomes in HCC. Recent advances in next-generation sequencing-based multi-omic and single cell analysis technologies have enabled us to develop high-resolution atlases of tumors and pull back the curtain on tumor heterogeneity. By combining multiregion targeting sampling strategies with deep sequencing of the genome, transcriptome, epigenome, and proteome, several studies have revealed novel mechanistic insights into tumor initiation and progression in HCC. Advances in multiparametric immune cell profiling have facilitated a deeper dive into the biological complexity of HCC, which is crucial in this era of immunotherapy. Moreover, studies using liquid biopsy have demonstrated their potential to circumvent the need for tissue sampling to investigate heterogeneity. In this review, we discuss how multi-omic and single-cell sequencing technologies have advanced our understanding of tumor heterogeneity in HCC.

Genomic Drivers in Breast Cancers

2016 ◽  
Vol 12 (01) ◽  
pp. 28
Author(s):  
Luis Teixeira ◽  
Françoise Rothé ◽  
Christos Sotiriou ◽  
◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Liquid Biopsy ◽  
Targeted Drugs ◽  
Breast Cancers ◽  
Genomic Alterations ◽  
Sequencing Technologies ◽  
Circulating Tumour Dna ◽  
Generation Sequencing

Significant advances in next-generation sequencing technologies have allowed the identification of genomic alterations in breast cancer. These alterations offer the opportunity to conduct studies with targeted drugs. However, there are still several scientific challenges to be addressed before precision medicine is widely used in the clinic. Nonetheless, different solutions are developed to overcome these obstacles such as the improvement of bioinformatics tools and the use of “liquid biopsy” to assess circulating tumour DNA.

scholarly journals Liquid Biopsy in Glioblastoma: Opportunities, Applications and Challenges

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 950 ◽  
Author(s):  
Saenz-Antoñanzas ◽  
Auzmendi-Iriarte ◽  
Carrasco-Garcia ◽  
Moreno-Cugnon ◽  
Ruiz ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Minimally Invasive ◽  
Liquid Biopsy ◽  
Medical Oncology ◽  
Invasive Procedure ◽  
Adult Brain ◽  
Disease Classification ◽  
Minimally Invasive Procedure ◽  
Similar Information ◽  
Tumor Profiling

Liquid biopsy represents a minimally invasive procedure that can provide similar information from body fluids to what is usually obtained from a tissue biopsy sample. Its implementation in the clinical setting might significantly renew the field of medical oncology, facilitating the introduction of the concepts of precision medicine and patient-tailored therapies. These advances may be useful in the diagnosis of brain tumors that currently require surgery for tissue collection, or to perform genetic tumor profiling for disease classification and guidance of therapy. In this review, we will summarize the most recent advances and putative applications of liquid biopsy in glioblastoma, the most common and malignant adult brain tumor. Moreover, we will discuss the remaining challenges and hurdles in terms of technology and biology for its clinical application.

scholarly journals Liquid biopsies and cancer omics

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Ivano Amelio ◽  
Riccardo Bertolo ◽  
Pierluigi Bove ◽  
Oreste Claudio Buonomo ◽  
Eleonora Candi ◽  
...  
Keyword(s):  
Tumor Heterogeneity ◽  
Molecular Data ◽  
Dependent Manner ◽  
Cancer Evolution ◽  
Dynamic Nature ◽  
Liquid Biopsies ◽  
Sequencing Technologies ◽  
Cancer Pathogenesis ◽  
Single Cancer ◽  
Cancer Specimen

AbstractThe development of the sequencing technologies allowed the generation of huge amounts of molecular data from a single cancer specimen, allowing the clinical oncology to enter the era of the precision medicine. This massive amount of data is highlighting new details on cancer pathogenesis but still relies on tissue biopsies, which are unable to capture the dynamic nature of cancer through its evolution. This assumption led to the exploration of non-tissue sources of tumoral material opening the field of liquid biopsies. Blood, together with body fluids such as urines, or stool, from cancer patients, are analyzed applying the techniques used for the generation of omics data. With blood, this approach would allow to take into account tumor heterogeneity (since the circulating components such as CTCs, ctDNA, or ECVs derive from each cancer clone) in a time dependent manner, resulting in a somehow “real-time” understanding of cancer evolution. Liquid biopsies are beginning nowdays to be applied in many cancer contexts and are at the basis of many clinical trials in oncology.

scholarly journals GENE-01. THE MUTATIONAL LANDSCAPE OF PRIMARY CHORDOMAS AND THEIR SENSITIVE DETECTION IN PLASMA ctDNA BY MULTIPLE NEXT GENERATION SEQUENCING TECHNOLOGIES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Austin Mattox ◽  
Yuchen Jiao ◽  
Cherie Blair ◽  
Nickolas Papadopoulos ◽  
Chetan Bettegowda
Keyword(s):  
Liquid Biopsy ◽  
Clinical Status ◽  
Spinal Column ◽  
Digital Pcr ◽  
Disease Recurrence ◽  
Blood Draw ◽  
Tumor Seeding ◽  
Mutational Landscape ◽  
Sequencing Technologies

Abstract CNS-associated tumors are notoriously difficult to detect in plasma. Chordomas are the most common primary spinal column malignancy, and extensive surgical procedures, along with chemotherapy and radiation are required to reduce recurrence. Currently CT, MRI, and PET are used to monitor for recurrence but are limited by surgical sequalae. In addition, needle biopsy risks tumor seeding along the biopsy track. In the largest cohort of chordomas described thus far, we characterize the mutational landscape of these tumors and show that liquid biopsy is a sensitive method for detecting cancers. 34 patients with a biopsy-confirmed diagnosis of chordoma had blood drawn before surgery, at the time of surgery, and/or at follow up appointments. Mutations in the primary tumor were identified by whole exome sequencing (WES) and droplet digital PCR (ddPCR) and/or Rapid Amplification of cDNA Ends Sequencing (RACE-Seq) was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points. The primary endpoint was detection of mutations in ctDNA in biopsy-confirmed chordoma samples. 87.9% of patients were ctDNA positive at the time of initial blood draw (p < 0.001). Follow up blood draws in twenty of the patients demonstrated that ctDNA levels reflected the clinical status of the disease. Patients with positive ctDNA levels were more likely to undergo radiotherapy (p = 0.004), and the presence of ctDNA may predict response to systemic chemotherapy and/or disease recurrence. Given the significant sequelae of biopsy and spinal surgery, liquid biopsy may be the best tool for detection and monitoring of chordomas.

The Influence of Memory-Aware Computation on Distributed BLAST

2019 ◽  
Vol 14 (2) ◽  
pp. 157-163
Author(s):  
Majid Hajibaba ◽  
Mohsen Sharifi ◽  
Saeid Gorgin
Keyword(s):  
Search Time ◽  
Genomic Research ◽  
Local Alignment ◽  
Negative Effects ◽  
Sequencing Technologies ◽  
Percent Improvement ◽  
Fast Processing ◽  
Search Tool ◽  
Memory Awareness ◽  
Generation Sequencing

Background: One of the pivotal challenges in nowadays genomic research domain is the fast processing of voluminous data such as the ones engendered by high-throughput Next-Generation Sequencing technologies. On the other hand, BLAST (Basic Local Alignment Search Tool), a longestablished and renowned tool in Bioinformatics, has shown to be incredibly slow in this regard. Objective: To improve the performance of BLAST in the processing of voluminous data, we have applied a novel memory-aware technique to BLAST for faster parallel processing of voluminous data. Method: We have used a master-worker model for the processing of voluminous data alongside a memory-aware technique in which the master partitions the whole data in equal chunks, one chunk for each worker, and consequently each worker further splits and formats its allocated data chunk according to the size of its memory. Each worker searches every split data one-by-one through a list of queries. Results: We have chosen a list of queries with different lengths to run insensitive searches in a huge database called UniProtKB/TrEMBL. Our experiments show 20 percent improvement in performance when workers used our proposed memory-aware technique compared to when they were not memory aware. Comparatively, experiments show even higher performance improvement, approximately 50 percent, when we applied our memory-aware technique to mpiBLAST. Conclusion: We have shown that memory-awareness in formatting bulky database, when running BLAST, can improve performance significantly, while preventing unexpected crashes in low-memory environments. Even though distributed computing attempts to mitigate search time by partitioning and distributing database portions, our memory-aware technique alleviates negative effects of page-faults on performance.

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