Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

Vietsch, Eveline E.; Graham, Garrett T.; McCutcheon, Justine N.; Javaid, Aamir; Giaccone, Giuseppe; Marshall, John L.; Wellstein, Anton

doi:10.1016/j.cancergen.2017.08.006

Cited by 49 publications

(49 citation statements)

References 29 publications

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“…The presence of the KRAS G12 mutation was associated with tumor responses observed on CT images in 76.9% of patients and provided the earliest measurement of treatment in 60%. Vietsch et al 62 analyzed the plasma of five PDAC patients at initial diagnosis with next-generation sequencing. An average of eight mutations was detected per sample, but concordance with the tumor sample was only 28%.…”

Section: Cfdna 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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Section: Cfdna 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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“…Accumulating evidence demonstrated that genetic mutations are associated with the occurrence and prognosis of tumors (34)(35)(36), including HCC (37)(38)(39). In the present study, it was identified that mutations in miRNA-424 target genes were associated with biological features of HCC.…”

Section: Discussionmentioning

confidence: 48%

Bioinformatics analysis of the interactions among lncRNA, miRNA and mRNA expression, genetic mutations and epigenetic modifications in hepatocellular carcinoma

Lin

Yuan

et al. 2018

Mol Med Report

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The present study aimed to investigate the regulatory networks involving long noncoding RNA (lncRNA), microRNA (miRNA), mRNA, genetic mutations and epigenetic modifications in hepatocellular carcinoma (HCC) by analyzing datasets from The Cancer Genome Atlas (TCGA) database. TCGA was mined, and miRNAs, lncRNAs and mRNAs that were differentially expressed in HCC were identified using R software. A gene regulatory network was constructed using Cytoscape software. Representative genes were selected for functional enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The associations among various proteins and protein networks were identified using the online software Search Tool for the Retrieval of Interacting Genes/Proteins. The cBioPortal database was used to analyze the association between genetic mutations and epigenetic modification, and the development of HCC. A total of 35 mRNAs were predicted to be targeted by 77 lncRNAs and 16 miRNAs, establishing a lncRNA-miRNA-mRNA regulatory network for HCC. Multivariable Cox regression analysis suggested that long intergenic non-protein coding RNA 200, miRNA-137, PDZ binding kinase and DNA polymerase θ were independent prognostic factors. In a regulatory network centered on miRNA-424, six mRNA target genes were associated with HCC survival rates. Protein-protein interaction analysis suggested that cell division cycle 25A (CDC25A) interacted with centrosomal protein 55 (CEP55), claspin, E2F transcription factor 7 and cyclin E1 (CCNE1. Mutations in CEP55 affected overall survival and disease-free survival in HCC, whereas, mutations in CDC25A affected overall survival, and mutations in E2F7 affected disease-free survival. Decreased methylation levels of CEP55, CDC25A and CCNE1 were associated with vascular invasion. The survival rate of patients with hypermethylation of CCNE1 and CEP55 was significantly associated with the rate of methylation of these loci. The present study provides an integrated bioinformatics analysis of gene expression, genetic mutations and epigenetic modifications that may be associated with the development of HCC.

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“…These mutations were within KRAS (n = 3), NRAS (n = 1), and BRAF (n = 1), and related to resistance of epidermal growth factor receptor blockade, which may contribute to chemotherapy selection. Some previous studies, including our own, reported that mutations not found in primary tumors could be detected in ccfDNA of CRC patients . However, detection of mutations in ctcDNA that were not found in primary tumors has only been reported in breast cancer patients .…”

Section: Discussionmentioning

confidence: 78%

“…Some previous studies, including our own, 2 reported that mutations not found in primary tumors could be detected in ccfDNA of CRC patients. 18,19 However, detection of mutations in ctcDNA that were not found in primary tumors has only been reported in breast cancer patients. 20,21 Recently, cancer has been considered to be a more heterogeneous disease than previously thought, 22 and discordance between primary and metastatic tumors has been reported.…”

Section: Discussionmentioning

confidence: 99%

Analysis of colorectal cancer‐related mutations by liquid biopsy: Utility of circulating cell‐free DNA and circulating tumor cells

et al. 2019

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We recruited 56 colorectal cancer patients and compared the mutational spectrum of tumor tissue DNA, circulating cell‐free DNA (ccfDNA) and circulating tumor cell (CTC) DNA (ctcDNA) to evaluate the potential of liquid biopsy to detect heterogeneity of cancer. Tumor tissue DNA, ccfDNA, and ctcDNA were extracted from each patient and analyzed using next‐generation sequencing (NGS) and digital PCR. To maximize yields of CTC, three antibodies were used in the capture process. From 34 untreated patients, 53 mutations were detected in tumor tissue DNA using NGS. Forty‐seven mutations were detected in ccfDNA, including 20 not detected in tissues. Sixteen mutations were detected in ctcDNA, including five not detected in tissues. In 12 patients (35.3%), mutations not found in tumor tissues were detected by liquid biopsy: nine (26.5%) in ccfDNA only and three (8.8%) in ctcDNA only. Combination analysis of the two liquid biopsy samples increased the sensitivity to detect heterogeneity. From 22 stage IV patients with RAS mutations in their primary tumors, RAS mutations were detected in 14 (63.6%) ccfDNA and in eight (36.4%) ctcDNA using digital PCR. Mutations not detected in primary tumors can be identified in ccfDNA and in ctcDNA, indicating the potential of liquid biopsy in complementing gene analysis. Combination analysis improves sensitivity. Sensitivity to detect cancer‐specific mutations is higher in ccfDNA compared with ctcDNA.

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Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

Cited by 49 publications

References 29 publications

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

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

Bioinformatics analysis of the interactions among lncRNA, miRNA and mRNA expression, genetic mutations and epigenetic modifications in hepatocellular carcinoma

Analysis of colorectal cancer‐related mutations by liquid biopsy: Utility of circulating cell‐free DNA and circulating tumor cells

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