Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients

Roy, Nadine Van; Linden, Malaïka Van Der; Menten, Björn; Dheedene, Annelies; Vandeputte, Charlotte; Dorpe, Jo Van; Laureys, Geneviève; Renard, Marleen; Sante, Tom; Lammens, Tim; Wilde, Bram De; Speleman, Franki; Preter, Katleen De

doi:10.1158/1078-0432.ccr-17-0675

Cited by 111 publications

(103 citation statements)

References 54 publications

(69 reference statements)

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“…This study revealed chromosome arm gains and losses, high level copy number gains, fusions and SNVs indicated in the pathogenesis of prostate cancer, therefore the timely and costly deep coverage WGS may be avoidable. Finally, the use of either the same analysis platform for both cfDNA and tumour or analysing all samples on both platforms may reduce the discordance rates attributed to differences in sensitivity [55].…”

Section: Detection Methodsmentioning

confidence: 99%

“…Figure 1 shows processing of cfDNA and primary and metastatic tumour tissue from sampling to analysis and the summary of contributing factors to discordance rates observed between SGAs in cfDNA and tumour tissue. A range of SGAs including numerical chromosome alterations (NCAs), segmental chromosome alterations (SCAs) and large SCAs have been investigated in cfDNA in neuroblastoma patients [53][54][55]. Chicard et al, inferred CNAs (including large SCAs, SCAs and NCAs) in cfDNA and matched tumour tissue of neuroblastoma patients.…”

Section: The Underlying Factors Contributing To Perceived Discordancementioning

confidence: 99%

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Assessing the Concordance of Genomic Alterations between Circulating-Free DNA and Tumour Tissue in Cancer Patients

Jahangiri

Hurst

2019

Cancers

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Somatic alterations to the genomes of solid tumours, which in some cases represent actionable drivers, provide diagnostic and prognostic insight into these complex diseases. Spatial and longitudinal tracking of somatic genomic alterations (SGAs) in patient tumours has emerged as a new avenue of investigation, not only as a disease monitoring strategy, but also to improve our understanding of heterogeneity and clonal evolution from diagnosis through disease progression. Furthermore, analysis of circulating-free DNA (cfDNA) in the so-called “liquid biopsy” has emerged as a non-invasive method to identify genomic information to inform targeted therapy and may also capture the heterogeneity of the primary and metastatic tumours. Considering the potential of cfDNA analysis as a translational laboratory tool in clinical practice, establishing the extent to which cfDNA represents the SGAs of tumours, particularly actionable driver alterations, becomes a matter of importance, warranting standardisation of methods and practices. Here, we assess the utilisation of cfDNA for molecular profiling of SGAs in tumour tissue across a broad range of solid tumours. Moreover, we examine the underlying factors contributing to discordance of detected SGAs between cfDNA and tumour tissue.

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Section: Detection Methodsmentioning

confidence: 99%

Section: The Underlying Factors Contributing To Perceived Discordancementioning

confidence: 99%

Assessing the Concordance of Genomic Alterations between Circulating-Free DNA and Tumour Tissue in Cancer Patients

Jahangiri

Hurst

2019

Cancers

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“…Especially, ultradeep duplex sequencing for mutation calling appears to be a promising approach; however, it remains expensive, requires targeted panels, and is yet to be extensively validated for its clinical use [10]. Shallow (coverage 0.1-0.5×) whole-genome sequencing (sWGS), on the other hand, has been shown to reliably detect copy number alterations (CNAs) in cfDNA [11][12][13]. As for single nucleotide polymorphisms (SNPs), specific CNAs are widely described to correlate with diagnosis in lung cancer [14].…”

Section: (Continued From Previous Page)mentioning

confidence: 99%

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma

et al. 2020

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Background: Accurate lung cancer classification is crucial to guide therapeutic decisions. However, histological subtyping by pathologists requires tumor tissue-a necessity that is often intrinsically associated with procedural difficulties. The analysis of circulating tumor DNA present in minimal-invasive blood samples, referred to as liquid biopsies, could therefore emerge as an attractive alternative. Methods: Concerning adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, our proof of concept study investigates the potential of liquid biopsy-derived copy number alterations, derived from single-end shallow whole-genome sequencing (coverage 0.1-0.5×), across 51 advanced stage lung cancer patients. Results: Genomic abnormality testing reveals anomalies in 86.3% of the liquid biopsies (16/20 for adenocarcinoma, 13/16 for squamous cell, and 15/15 for small cell carcinoma). We demonstrate that copy number profiles from formalin-fixed paraffin-embedded tumor biopsies are well represented by their liquid equivalent. This is especially valid within the small cell carcinoma group, where paired profiles have an average Pearson correlation of 0.86 (95% CI 0.79-0.93). A predictive model trained with public data, derived from 843 tissue biopsies, shows that liquid biopsies exhibit multiple deviations that reflect histological classification. Most notably, distinguishing small from non-small cell lung cancer is characterized by an area under the curve of 0.98 during receiver operating characteristic analysis. Additionally, we investigated how deeper paired-end sequencing, which will eventually become feasible for routine diagnosis, empowers tumor read enrichment by insert size filtering: for all of the 29 resequenced liquid biopsies, the tumor fraction could be increased in silico, thereby "rescuing" three out of five cases with previously undetectable alterations.(Continued on next page)

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“…Other efforts exploring cell-free DNA in pediatric cancer have focused on detection of copy number aberrations, structural variants 32,33 and mutations 34 . However, these alterations come with low specificity for classification of pediatric solid tumors according to their histopathological diagnosis 35 .…”

Section: Discussionmentioning

confidence: 99%

Minimally invasive classification of pediatric solid tumors using reduced representation bisulfite sequencing of cell-free DNA: a proof-of-principle study

Paemel

Koker

Vandeputte

et al. 2019

Preprint

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In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA.Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner. Translational relevanceObtaining a correct diagnosis in pediatric oncology can be challenging in some tumor types, especially in renal tumors or central nervous system tumors. Furthermore, the diagnostic odyssey can result in anxiety and discomfort for these children. By applying a novel technique, reduced representation bisulfite sequencing on cell-free DNA (cf-RRBS), we show the feasibility of obtaining the histopathological diagnosis with a minimally invasive test on either plasma or cerebrospinal fluid. Furthermore, we were able to derive the copy number profile or tumor subtype from the same assay. Given that primary tumor material might be difficult to obtain, in particular in critically ill children or depending on the tumor location, and might be limited in terms of quantity or quality, our assay could become complementary to the classical tissue biopsy in difficult cases.

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Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients

Cited by 111 publications

References 54 publications

Assessing the Concordance of Genomic Alterations between Circulating-Free DNA and Tumour Tissue in Cancer Patients

Assessing the Concordance of Genomic Alterations between Circulating-Free DNA and Tumour Tissue in Cancer Patients

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma

Minimally invasive classification of pediatric solid tumors using reduced representation bisulfite sequencing of cell-free DNA: a proof-of-principle study

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