Accessing Genetic Information with Liquid Biopsies

Cai, Xinjiang; Janků, Filip; Zhan, Qimin; Fan, Jie

doi:10.1016/j.tig.2015.06.001

Cited by 131 publications

(85 citation statements)

References 71 publications

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“…These duplicates were filtered out during the bioinformatics analysis pipeline, but it cannot be excluded that some identical reads not corresponding to PCR duplicates are also falsely removed. Thus, this protocol could be further improved using a UMI (unique molecular identifiers) prior to library construction to separate real PCR duplicates from alignment duplicates (47).…”

Section: Discussionmentioning

confidence: 99%

Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma

Chicard

Colmet‐Daage

Clément

et al. 2018

Clinical Cancer Research

124

152

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Purpose: Neuroblastoma displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression.Experimental Design: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole-exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 neuroblastoma patients.Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of single-nucleotide variants (SNV) and copy number alterations, with 41% and 93% of all detected alterations common to the primary neuroblastoma and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate time points during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2.Conclusions: Modelization of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating toward tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies. Clin Cancer Res; 1-11. Ó2017 AACR.

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Section: Discussionmentioning

confidence: 99%

Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma

Chicard

Colmet‐Daage

Clément

et al. 2018

Clinical Cancer Research

124

152

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“…in serum (Liu et al, 2011). Molecular 'liquid biopsies' are quickly moving into the clinic, creating a new palette of molecular diagnostics and becoming a central piece in the future of platform technology for precision medicine (Cai et al, 2015). Circulating biodosimetry markers collected from liquid biopsies are especially helpful to assess the dose of absorbed radiation in the case of an accidental exposure to IR requiring fast and efficient triage for guiding medical countermeasures.…”

Section: Ionizing Radiation Increases Mir-34a Expressionmentioning

confidence: 99%

Emergence of miR-34a in radiation therapy

Lacombe

Zenhausern

2017

Critical Reviews in Oncology/Hematology

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Expressions of many microRNAs (miRNAs) in response to ionizing radiation (IR) have already been investigated and some of them seem to play an important role in the tumor radioresistance, normal tissue radiotoxicity or as predictive biomarkers to radiation. MiR-34a is an emerging miRNA in recent radiobiology studies. Here, we review this miR-34 family member by detailing its different roles in radiation response and we will discuss about the role that it can play in radiation treatment. Thus, we will show that IR regulates miR-34a by increasing its expression. We will also highlight different biological processes involved in cellular response to IR and regulated by miR-34a in order to demonstrate the role it can play in tumor radio-response or normal tissue radiotoxicity as a radiosensitizer or radioprotector. MiR-34a is poised to assert itself as an important player in radiobiology and should become more and more important in radiation therapy management.

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“…With the rapid development of highly sensitive and accurate technologies of NGS, it can not only predict the response to treatment, but also monitor minimal residual disease [69,70]. As an example, FGFR2 fusion in ctDNA was readily detectable by quantitative realtime reverse transcription-polymerase chain reaction and corroborated to be more sensitive and specific than previous biomarkers, such as CA125 [71].…”

Section: Perspectivementioning

confidence: 98%

Fusion Genes and their Detection through Next Generation Sequencing in Malignant Hematological Disease and Solid Tumors

Liu¹,

Weng²,

Ming³

et al. 2016

Diagn Pathol Open

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Fusion genes are neoplasia-associated mutations, which play a particularly significant role in tumorgenesis and exhibit great importance for clinical applications in malignant hematological diseases and solid tumors. Simultaneously with copy number variants (CNVs), gene fusions are resulting from balanced and unbalanced chromosomal rearrangements. Thus, understanding the mutagenesis and instability of CNV, as well as the underlying molecular mechanisms of chromosomal rearrangements will improve our comprehension of gene fusions. Recently, next generation sequencing (NGS), especially transcriptome sequencing or RNA-Sequencing (RNA-seq), has become a very useful tool to identify gene alterations in cancer and a powerful approach for investigating the tumorgenesis. However, we are still facing with the challenge of minimizing false positives in results of RNA-seq. Whole-genome sequencing (WGS) is also used for the fusion gene detection, which provides us a more comprehensive and integrative way to detect structural variants. WGS may correct the false-negative results from RNA-seq. Additionally; many computational tools with more sensitivity and specificity have been developed for the detection of fusion transcripts from NGS datas. In the future, multi-omics analysis, third-generation sequencing and liquid-biopsy technique all provide opportunities to comprehensively interpret gene fusions and understand the biology of cancer genomes.

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Accessing Genetic Information with Liquid Biopsies

Cited by 131 publications

References 71 publications

Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma

Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma

Emergence of miR-34a in radiation therapy

Fusion Genes and their Detection through Next Generation Sequencing in Malignant Hematological Disease and Solid Tumors

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