scholarly journals Prognostic impact of KRAS mutation in cell-free DNA in patients with pancreatic cancer

2017 ◽  
Vol 28 ◽  
pp. v9
Author(s):  
M.K. Kim ◽  
S.M. Woo ◽  
B. Park ◽  
K-A. Yoon ◽  
Y.H. Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Kras Mutation ◽  
Prognostic Impact ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1599
Author(s):  
Eunsung Jun ◽  
Bonhan Koo ◽  
Eo Jin Kim ◽  
Dae Wook Hwang ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Significance ◽  
Kras Mutation ◽  
Predictive Marker ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Cell Free Dna ◽  
Cancer Subtypes ◽  
Free Dna ◽  
Mutation Burden

KRAS mutation is a major regulator in the tumor progression of pancreatic cancer. Here, we compared the frequency and mutation burden of KRAS mutation subtypes with paired tumor tissue and blood in patients and examined their clinical significance. DNA from tumor tissues and cell-free DNA (cfDNA) from preoperative blood were obtained from 70 patients with pancreatic cancer. Subtypes and mutation burdens of KRAS G12D and G12V mutations were evaluated using droplet digital PCR. Comparing the presence of mutations in tissue, accumulative and simultaneous mutations of G12D or G12V were identified of 67 (95.7%), and 48 patients (68.6%). Conversely, in blood, they were only identified in 18 (25.7%) and four (5.7%) patients; respectively. Next, comparing the mutation burden in tissue, the mutation burden varied from less than 0.1 to more than five, whereas that of cfDNA in blood was mostly between one and five, as cases with a mutation burden lower than 0.1 and higher than five were rare. Finally, the presence of the G12V mutation alone in cfDNA and the combination of the G12V mutation with elevated CA 19-9 levels were associated with poor recurrence-free survival. These fundamental data on the KRAS mutation subtypes and their clinical significance could support their potential as predictive markers for postoperative recurrence.

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

EBioMedicine ◽  
2019 ◽  
Vol 41 ◽  
pp. 345-356 ◽  
Author(s):  
Xiaoyu Liu ◽  
Lingxiao Liu ◽  
Yuan Ji ◽  
Changyu Li ◽  
Tao Wei ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mutant Cell ◽  
Dna Fragments ◽  
Cell Free Dna ◽  
Free Dna

Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV detection in plasma

2013 ◽  
Vol 13 (5) ◽  
pp. 385-394 ◽  
Author(s):  
Agnieszka M. Mazurek ◽  
A. Fiszer-Kierzkowska ◽  
T. Rutkowski ◽  
K. Składowski ◽  
M. Pierzyna ◽  
...  
Keyword(s):  
Kras Mutation ◽  
Cell Free Dna ◽  
Dna Recovery ◽  
Free Dna ◽  
Circulating Cell Free Dna

scholarly journals Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gulfem D. Guler ◽  
Yuhong Ning ◽  
Chin-Jen Ku ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Cell Free Dna ◽  
Early Stage Disease ◽  
Non Invasive ◽  
Cancer Pathogenesis ◽  
Free Dna ◽  
Stage Disease ◽  
Circulating Cell Free Dna

Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.

scholarly journals Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA

EBioMedicine ◽  
2020 ◽  
Vol 55 ◽  
pp. 102462 ◽  
Author(s):  
Maria Zvereva ◽  
Gabriel Roberti ◽  
Geoffroy Durand ◽  
Catherine Voegele ◽  
Minh Dao Nguyen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 64 (4) ◽  
pp. 726-734 ◽  
Author(s):  
Min Kyeong Kim ◽  
Sang Myung Woo ◽  
Boram Park ◽  
Kyong-Ah Yoon ◽  
Yun-Hee Kim ◽  
...  
Keyword(s):  
Kras Mutation ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Multiplex Detection ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Free Survival ◽  
Free Dna ◽  
Fractional Abundance ◽  
Prognostic Implications

Abstract BACKGROUND Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. METHODS A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). RESULTS KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20–3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02–2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05–3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. CONCLUSIONS This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.

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