Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

Sefrioui, David; Blanchard, F.; Touré, Emmanuel; Basile, Paul; Beaussire, Ludivine; Dolfus, Claire; Perdrix, A.; Paresy, Marianne; Antonietti, Michel; Iwanicki–Caron, Isabelle; Alhameedi, Raied; Lecleire, Stéphane; Gangloff, Alice; Schwarz, L.; Clatot, Florian; Tuech, Jean‐Jacques; Frébourg, Thierry; Jardin, Fabrice; Sabourin, Jean‐Christophe; Sarafan-Vasseur, Nasrin; Michel, Pierre; Fiore, Frédéric Di

doi:10.1038/bjc.2017.250

Cited by 93 publications

(88 citation statements)

References 44 publications

(62 reference statements)

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“…We compared the performance of our approach in measuring KRAS mutations with that in previous reports using PCR- or NGS-based methods ( Table S4 ). (Allenson et al, 2017; Berger et al, 2016; Brychta et al, 2016; Cheng et al, 2017; Cohen et al, 2017; Hadano et al, 2016; Kim et al, 2018; Kinugasa et al, 2015; Le Calvez-Kelm et al, 2016; Pietrasz et al, 2017; Sausen et al, 2015; Sefrioui et al, 2017; Takai et al, 2015) Across 13 high-quality studies, the detection rate of the KRAS mutations in plasma ranged from to 21% to 76% ( Fig. 2A ).…”

Section: Resultsmentioning

confidence: 99%

Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer

Liu

et al. 2018

Preprint

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30Analysis of cell-free DNA (cfDNA) is promising for broad applications in clinical 31 settings, but with significant bias towards late-stage cancers. Although recent studies have 32 discussed the diverse and degraded nature of cfDNA molecules, little is known about its 33 impact on the practice of cfDNA analysis. Here we reported a new targeted sequencing by 34 combining single-strand library preparation and target capture (SLHC-seq). By applying 35 the new technology in plasma cfDNA from pancreatic cancer patients, we achieved higher 36 efficiency in analysis of mutations than previously reported using other detection assays. 37 SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity 38 and accuracy of circulating-tumor DNA detection. Most importantly, we found that the 39 small mutant fragments are prevalent in early-stage patients, which provides strong 40 evidence for fragment size-based early detection of pancreatic cancer. Collectively, the 41 new pipeline enhanced our understanding of cfDNA biology and provide new insights for 42 liquid biopsy. 43 44 MAIN TEXT 45 65 sequencing.(Aravanis et al, 2017; Zill et al, 2015) Moreover, the noninvasive nature of cfDNA 66 analysis enables doctors to monitor disease progression.(Couraud et al, 2014; Murtaza et al, 2013; 67 Zill et al, 2015) However, cfDNA analysis using large-scale next-generation sequencing (NGS) 68 has been largely confined to advanced or metastatic cancers, in which the ctDNA ( circulating-69 tumor DNA ) fraction is higher and is more readily detectable.(Gorgannezhad et al, 2018; Haber 70 & Velculescu, 2014) Detection of ctDNA in early-stage cancers is still filled with cautionary tales 71 that highlight the technical challenges in this field. Recently, Velculescu et al reported improved 72 targeted error correction sequencing ( TEC-Seq ) as an efficient approach for the detection of 73 ctDNA in early-stage colorectal, ovarian, breast, and lung cancers, with a detection rate ranging 74 from 59% to 71%.(Phallen et al, 2017) The massive parallel sequencing approach provides an 75 applicable paradigm guiding cfDNA analysis in early-stage cancers. 76 However, the performance of existing approaches is limited in cfDNA analysis in early-77 stage pancreatic cancers. This limitation may be partially because of a lower ctDNA content in 78 the circulation of pancreatic cancers.(Aravanis et al, 2017) Moreover, the biological features of 79

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Section: Resultsmentioning

confidence: 99%

Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer

Liu

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…For this reason, CTCs do not currently have a high enough sensitivity to be used for diagnosis, as a liquid biopsy. Certainly, only a sensitivity of 67% was found when distinguishing PDAC from other malignant pancreatic tumors 26 ; and a sensitivity of 68% was found for distinguishing between PDAC and other pancreatic disease or healthy patients, including pancreatic pseudocysts, pancreatic serous cystadenomas, and solid pseudopapillary tumors. 37 Indeed, CTCs have also been identified in 63% of those with benign disease, 28 33% of patients with benign cystic lesions, 41 64% with neuroendocrine tumors, 62% with intraductal papillary mucinous neoplasms, and 46% with chronic pancreatitis, 36 implying a low specificity.…”

Section: Ctc Detection In Pancreatic Cancermentioning

confidence: 99%

Circulating Tumor Cells and Cell-Free DNA in Pancreatic Ductal Adenocarcinoma

Gall

Belete

Khanderia

et al. 2019

The American Journal of Pathology

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Pancreatic cancer is detected late in the disease process and has an extremely poor prognosis. A bloodbased biomarker that can enable early detection of disease, monitor response to treatment, and potentially allow for personalized treatment would be of great benefit. This review analyzes the literature regarding two potential biomarkers, circulating tumor cells (CTCs) and cell-free DNA (cfDNA), with regard to pancreatic ductal adenocarcinoma. The origin of CTCs and the methods of detection are discussed and a decade of research examining CTCs in pancreatic cancer is summarized, including both levels of CTCs and analyzing their molecular characteristics and how they may affect survival in both advanced and early disease and allow for treatment monitoring. The origin of cfDNA is discussed, and the literature over the past 15 years is summarized. This includes analyzing cfDNA for genetic mutations and methylation abnormalities, which have the potential to be used for the detection and prognosis of pancreatic ductal adenocarcinoma. However, the research certainly remains in the experimental stage, warranting future large trials in these areas. (Am J Pathol 2019, 189: 71e81; https://doi.

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“…Liquid biopsies for circulating tumor cells or ctDNA constitute a promising and less invasive technique. [4][5][6][7][8][9][10] ctDNA is circulating cfDNA derived from tumor cells. However, no satisfactory blood-based markers for RCC currently exist, creating an urgent need for the identification of new molecular markers.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of the mutational landscape and fragmentation of circulating tumor DNA in renal cell carcinoma

et al. 2019

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Reliable biomarkers for renal cell carcinoma (RCC) have yet to be determined. Circulating tumor DNA (ctDNA) is an emerging resource to detect and monitor molecular characteristics of various tumors. The present study aims to clarify the clinical utility of ctDNA for RCC. Fifty‐three patients histologically diagnosed with clear cell RCC were enrolled. Targeted sequencing was carried out using plasma cell‐free DNA (cfDNA) and tumor DNA. We applied droplet digital PCR (ddPCR) to validate detected mutations. cfDNA fragment size was also evaluated using a microfluidics‐based platform and sequencing. Proportion of cfDNA fragments was defined as the ratio of small (50‐166 bp) to large (167‐250 bp) cfDNA fragments. Association of mutant allele frequency of ctDNA with clinical course was analyzed. Prognostic potential was evaluated using log‐rank test. A total of 38 mutations across 16 (30%) patients were identified from cfDNA, including mutations in TP53 (n = 6) and VHL (n = 5), and median mutant allele frequency of ctDNA was 10%. We designed specific ddPCR probes for 11 mutations and detected the same mutations in both cfDNA and tumor DNA. Positive ctDNA was significantly associated with a higher proportion of cfDNA fragments (P = .033), indicating RCC patients with ctDNA had shorter fragment sizes of cfDNA. Interestingly, the changes of mutant allele frequency in ctDNA concurrently correlated with clinical course. Positive ctDNA and fragmentation of cfDNA were significantly associated with poor cancer‐specific survival (P < .001, P = .011). In conclusion, our study shows the clinical utility of ctDNA status and cfDNA fragment size as biomarkers for prognosis and disease monitoring in RCC.

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Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours

Cited by 93 publications

References 44 publications

Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer

Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer

Circulating Tumor Cells and Cell-Free DNA in Pancreatic Ductal Adenocarcinoma

Clinical significance of the mutational landscape and fragmentation of circulating tumor DNA in renal cell carcinoma

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