Genome‐wide profiling of circulating tumor DNA depicts landscape of copy number alterations in pancreatic cancer with liver metastasis

Tao, Wei; Zhang, Jian; Li, Jin; Chen, Qi; Zhi, Xiaoqin; Ma, Jingjiao; Yang, Jiaqi; Lou, Yiting; Ma, Tao; Li, Xiang; Zhang, Qi; Chen, Wei; Que, Risheng; Gao, Shunliang; Bai, Xueli; Liang, Tingbo

doi:10.1002/1878-0261.12757

Cited by 12 publications

(20 citation statements)

References 43 publications

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“…In total, 42 studies measured the cfDNA in plasma [ 9 , 13 , 21 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 34 , 35 , 36 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ], three studies measured it from serum [ 37 , 47 , 67 ], two studies measured it from blood [ 20 , 22 ] and one study examined the cfDNA both in serum and plasma [ 23 ]. The time of the sampling was pre-treatment in 29 studies [ 9 , 13 , 23 , 24 , …”

Section: Resultsmentioning

confidence: 99%

“…The time of the sampling was pre-treatment in 29 studies [ 9 , 13 , 23 , 24 , 26 , 29 , 34 , 36 , 37 , 38 , 39 , 40 , 43 , 44 , 46 , 49 , 52 , 53 , 54 , 55 , 57 , 58 , 60 , 62 , 63 , 64 , 65 , 66 , 67 ], pre/post-treatment in 10 studies [ 25 , 27 , 28 , 30 , 35 , 41 , 42 , 45 , 47 , 59 ], post-treatment only in two studies [ 48 , 50 ], pre/post and during treatment in one study [ 22 ], and six studies did not report the time of sampling [ 20 , 21 , 31 , 51 , 56 , 61 ]. KRAS was explicitly measured in 41 studies [ 9 , 20 , 21 , 22 ,…”

Section: Resultsmentioning

confidence: 99%

“…A total of 44 studies used polymerase chain reaction (PCR) (ddPCR in 24 [ 9 , 23 , 24 , 25 , 26 , 28 , 30 , 31 , 34 , 37 , 38 , 41 , 44 , 45 , 46 , 49 , 52 , 55 , 57 , 58 , 59 , 60 , 63 , 67 ]; two used restriction fragment length-PCR (RFLP-PCR) [ 36 , 54 ]; two used nested PCR [ 53 , 56 ]; two used peptide nucleic acid-mediated clamping (PNA clamping) [ 22 , 47 ]; three used beads, emulsions, amplification and magnetics (BEAMing) [ 27 , 50 , 64 ]; one used mutant allele-specific PCR (MASA PCR) [ 35 ]; one used amplification-refractory mutation system PCR (ARMS PCR) [ 21 ]; one used quantitative methylation specific polymerase chain reaction (qMSP PCR) [ 51 ]; and an explicit PCR method was not reported in eight studies [ 20 , 29 , 39 , 40 , 42 , 46 , 48 , 66 ]). Next-generation sequencing (NGS) was used in three studies [ 61 , 62 , 65 ], and a bioassay was used as a primary metho...…”

Section: Resultsmentioning

confidence: 99%

“…A total of 35 studies had OS as an outcome. Four studies were excluded from the overall HR effect size calculation due to measuring hypermethylation in ctDNA [ 40 ] or only post-treatment cfDNA, [ 48 , 50 ] or performing cfDNA TFx analysis [ 66 ]. Finally, 31 studies were included in the meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

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Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer

Milin-Lazović

Madzarevic

Rajović

et al. 2021

Cancers

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Introduction: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. Material and Methods: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients’ survival. The studies published before 22 October 2020 were identified through the PubMED, EMBASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. Results: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI: 1.95–2.99 and HR = 2.46, 95% CI: 2.01–3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90–3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02–27.63). Conclusion: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer

Milin-Lazović

Madzarevic

Rajović

et al. 2021

Cancers

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“…Relative differences in read count between bins can be sensitively detected even when the total read count is low [20, 21, 22], meaning that SCNAs can be detected with a fraction of the sequencing depth required for SNV detection. Therefore SCNA profiling offers a high-throughput and cost-effective means to evaluate cfDNA samples [23, 24, 25, 26, 27, 28].…”

Section: Introductionmentioning

confidence: 99%

LiquidCNA: tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations

Lakatos

Hockings

Mossner

et al. 2021

Preprint

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Cell-free DNA (cfDNA) measured via liquid biopsies provides a way for minimally-invasive monitoring of tumour evolutionary dynamics during therapy. Here we present liquidCNA, a method to track subclonal evolution from longitudinally collected cfDNA samples based on somatic copy number alterations (SCNAs). LiquidCNA utilises SCNA profiles derived through cost-effective low-pass whole genome sequencing to automatically and simultaneously genotype and quantify the size of the dominant subclone without requiring prior knowledge of the genetic identity of the emerging clone. We demonstrate the accuracy of liquidCNA in synthetically generated sample sets and in vitro and in silico mixtures of cancer cell lines. Application in vivo in patients with metastatic lung cancer reveals the progressive emergence of a novel tumour sub-population. LiquidCNA is straightforward to use, computationally inexpensive and enables continuous monitoring of subclonal evolution to understand and control therapy-induced resistance.

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Pan-Cancer Detection and Typing by Mining Patterns in Large Genome-Wide Cell-Free DNA Sequencing Datasets

et al. 2022

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Background Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis, and monitoring. We hypothesized that mining the patterns of cfDNA shallow whole-genome sequencing datasets from patients with cancer could improve cancer detection. Methods By applying unsupervised clustering and supervised machine learning on large cfDNA shallow whole-genome sequencing datasets from healthy individuals (n = 367) and patients with different hematological (n = 238) and solid malignancies (n = 320), we identified cfDNA signatures that enabled cancer detection and typing. Results Unsupervised clustering revealed cancer type-specific sub-grouping. Classification using a supervised machine learning model yielded accuracies of 96% and 65% in discriminating hematological and solid malignancies from healthy controls, respectively. The accuracy of disease type prediction was 85% and 70% for the hematological and solid cancers, respectively. The potential utility of managing a specific cancer was demonstrated by classifying benign from invasive and borderline adnexal masses with an area under the curve of 0.87 and 0.74, respectively. Conclusions This approach provides a generic analytical strategy for non-invasive pan-cancer detection and cancer type prediction.

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Genome‐wide profiling of circulating tumor DNA depicts landscape of copy number alterations in pancreatic cancer with liver metastasis

Cited by 12 publications

References 43 publications

Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer

Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer

LiquidCNA: tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations

Pan-Cancer Detection and Typing by Mining Patterns in Large Genome-Wide Cell-Free DNA Sequencing Datasets

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