Abstract 1372: Detection of early stage pancreatic cancer using 5–hydroxymethylcytosine signatures in circulating cell free DNA

2019 ◽  
Author(s):  
Francois Collin ◽  
Yuhong Ning ◽  
Gulfem D. Guler ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Cell Free Dna ◽  
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 Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

2018 ◽  
Author(s):  
Francois Collin ◽  
Yuhong Ning ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
Aaron Scott ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Training Data ◽  
Ductal Adenocarcinoma ◽  
Data Sets ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Pancreatic Cancers ◽  
Free Dna ◽  
Circulating Cell Free Dna

AbstractPancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial by enabling surgical resection or earlier application of therapeutic regimens. We investigated the detection of pancreatic ductal adenocarcinoma (PDAC) in a non-invasive manner by interrogating changes in 5-hydroxymethylation cytosine status (5hmC) of circulating cell free DNA in the plasma of a PDAC cohort (n=51) in comparison with a non-cancer cohort (n=41). We found that 5hmC sites are enriched in a disease and stage specific manner in exons, 3’UTRs and transcription termination sites. Our data show that 5hmC density is reduced in promoters and histone H3K4me3-associated sites with progressive disease suggesting increased transcriptional activity. 5hmC density is differentially represented in thousands of genes, and a stringently filtered set of the most significant genes points to biology related to pancreas (GATA4, GATA6, PROX1, ONECUT1) and/or cancer development (YAP1, TEAD1, PROX1, ONECUT1, ONECUT2, IGF1 and IGF2). Regularized regression models were built using 5hmC densities in statistically filtered genes or a comprehensive set of highly variable 5hmC counts in genes and performed with an AUC = 0.94-0.96 on training data. We were able to test the ability to classify PDAC and non-cancer samples with the Elastic net and Lasso models on two external pancreatic cancer 5hmC data sets and found validation performance to be AUC = 0.74-0.97. The findings suggest that 5hmC changes enable classification of PDAC patients with high fidelity and are worthy of further investigation on larger cohorts of patient samples.

Abstract 1372: Detection of early stage pancreatic cancer using 5–hydroxymethylcytosine signatures in circulating cell free DNA

2019 ◽  
Author(s):  
Francois Collin ◽  
Yuhong Ning ◽  
Gulfem D. Guler ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Cell Free Dna ◽  
Free Dna ◽  
Circulating Cell Free Dna

scholarly journals Probing of breast cancer using a combination of plasma and urinary circulating cell-free DNA

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Zhigang Zuo ◽  
Jiying Tang ◽  
Xiaojun Cai ◽  
Feng Ke ◽  
Zhenzong Shi
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Pik3ca Mutation ◽  
Early Stage Breast Cancer ◽  
Healthy Controls ◽  
Cell Free Dna ◽  
Clinical Sensitivity ◽  
Free Dna ◽  
Urine Specimens ◽  
Circulating Cell Free Dna

Abstract Monitoring of early-stage breast cancer is critical in promptly addressing disease relapse. Circulating cell-free DNA provides a minimally invasive and sensitive means to probing the disease. In a longitudinal analysis of 250 patients with early breast cancer, we compared the circulating cell-free DNA recovered from both plasma and urine specimens. For comparison, 50 healthy controls were also recruited. Specific mutations associated with the disease were profiled to determine the clinical sensitivity and specificity. Correlations of recovered concentrations of cell-free DNA with outcomes were examined to address early prognostication. PIK3CA mutation profiling in both plasma and urinary cell-free DNA showed an agreement of 97.2% compared with the results obtained for tumor tissues. The analysis of healthy controls revealed that cell-free DNA measurements were stable and consistent over time. Over the short 6-month period of monitoring, our analyses showed declines in recovered cell-free DNA; these findings may aid physicians in stratifying patients at higher risk for relapse. Similar results were observed in both plasma and urine specimens (hazard ratios: 2.16 and 2.48, respectively). Cell-free DNA presents a novel and sensitive method for the monitoring of early-stage breast cancer. In the present study, serial measurements of both plasma and urine specimens were useful in probing the disease.

scholarly journals Detection of Colorectal Cancer in Circulating Cell-Free DNA by Methylated CpG Tandem Amplification and Sequencing

2019 ◽  
Vol 65 (7) ◽  
pp. 916-926 ◽  
Author(s):  
Jingyi Li ◽  
Xin Zhou ◽  
Xiaomeng Liu ◽  
Jie Ren ◽  
Jilian Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Plasma Samples ◽  
Dna Hypermethylation ◽  
Cell Free Dna ◽  
Noncancerous Tissue ◽  
Clinical Sensitivity ◽  
Free Dna ◽  
A Genome ◽  
Circulating Cell Free Dna

Abstract BACKGROUND Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-wide DNA hypermethylation analysis technique using circulating cell-free DNA (cfDNA) is attractive for the noninvasive early detection of CRC and discrimination between CRC and other cancer types. METHODS We applied the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, with a fully methylated molecules algorithm, to plasma samples from patients with CRC (n = 147) and controls (n = 136), as well as cancer and adjacent noncancerous tissue samples (n = 66). We also comparatively analyzed plasma samples from patients with hepatocellular carcinoma (HCC; n = 36). RESULTS Dozens of DNA hypermethylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5, CHST11, APBB1IP, and TJP2) genes were identified for effectively detecting CRC in cfDNA. A panel of 80 markers discriminated early-stage CRC patients and controls with a clinical sensitivity of 74% and clinical specificity of 90%. Patients with early-stage CRC and HCC could be discriminated at clinical sensitivities of approximately 70% by another panel of 128 markers. CONCLUSIONS MCTA-Seq is a promising method for the noninvasive detection of CRC.

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

2018 ◽  
Author(s):  
Xiaoyu Liu ◽  
Lingxiao Liu ◽  
Yuan Ji ◽  
Changyu Li ◽  
Tao Wei ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Fragment Size ◽  
New Technology ◽  
Mutant Cell ◽  
Circulating Tumor Dna ◽  
Clinical Settings ◽  
Cell Free Dna ◽  
Free Dna ◽  
Target Capture

Analysis of cell-free DNA (cfDNA) is promising for broad applications in clinical settings, but with significant bias towards late-stage cancers. Although recent studies have discussed the diverse and degraded nature of cfDNA molecules, little is known about its impact on the practice of cfDNA analysis. Here we reported a new targeted sequencing by combining single-strand library preparation and target capture (SLHC-seq). By applying the new technology in plasma cfDNA from pancreatic cancer patients, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumor DNA detection. Most importantly, we found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based early detection of pancreatic cancer. Collectively, the new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy.

scholarly journals KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control

Oncotarget ◽  
2016 ◽  
Vol 7 (48) ◽  
pp. 78827-78840 ◽  
Author(s):  
Florence Le Calvez-Kelm ◽  
Matthieu Foll ◽  
Magdalena B. Wozniak ◽  
Tiffany M. Delhomme ◽  
Geoffroy Durand ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Case Control ◽  
Cancer Case ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Circulating Cell Free Dna
Sign in / Sign up

Export Citation Format

Share Document