Detection of Hot-Spot Mutations in Circulating Cell-Free DNA From Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas

Berger, Andreas W.; Schwerdel, Daniel; Costa, Ivan G.; Hackert, Thilo; Strobel, Oliver; Lam, Sandra; Barth, Thomas F.E.; Schröppel, Bernd; Meining, Alexander; Büchler, Markus W.; Zenke, Martin; Hermann, Patrick C.; Seufferlein, Thomas; Kleger, Alexander

doi:10.1053/j.gastro.2016.04.034

Cited by 78 publications

(68 citation statements)

References 16 publications

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“…First described in 1948, cfDNA has been analyzed for many years to test its potential as a noninvasive biomarker in cancer patients [13, 31, 33–37]. Patients with malignant tumors carry significantly more cfDNA compared to those with benign or premalignant lesions or healthy individuals, for example in pulmonary or gastrointestinal diseases [21, 38–42]. In this study, we confirm this concept in patients with metastatic CRC compared to healthy individuals.…”

Section: Discussionsupporting

confidence: 75%

“…This balance can be disturbed even upon benign tumorigenesis as recently shown by our group for patients with cystic pancreatic tumors, having significantly higher cfDNA levels compared to healthy individuals. Moreover, cfDNA has the potential to discriminate patients with benign and malignant pancreatic diseases [21] and thus confirms data from previous reports. Therefore, cfDNA could be a promising tool for repeated noninvasive tumor assessment in oncology [22].…”

Section: Introductionsupporting

confidence: 88%

“…Therefore, cfDNA quantification in therapy naïve patients allows to determine the tumor load in an easy noninvasive procedure. But comparisons between the various studies are difficult to make, not at least due to a lack of standardized procedures and technologies for isolation and quantification of cfDNA, like BEAMing, several quantitative real-time PCR protocols [27], ddPCR technologies [21, 30] or digital genomic assays, for example Safe-SeqS [28], resulting in a limited generalizability. Interestingly, cfDNA levels in our study did not correlate with tumor burden according to RECIST 1.1 criteria at disease progression under 1 st line and 2 nd treatment ( S1E and S1F Fig ).…”

Section: Discussionmentioning

confidence: 99%

“…Besides the quantitative assessment of cfDNA during the course of several chemotherapeutic regimens we focused on the molecular characterization of cfDNA by targeted genotyping of KRAS using droplet digital PCR (ddPCR), an established technology for this application [21, 30]. KRAS genotyping of cfDNA is not considered as a standard in metastatic CRC patients undergoing treatment with anti- EGFR antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…CEA measurements were performed in parallel to cfDNA analyses at baseline, staging and restaging time points. Additionally, cfDNA was compared to a previously reported [21] cohort of 38 healthy controls ( S2 Table ) without any chronic, malignant or inflammatory diseases.…”

Section: Methodsmentioning

confidence: 99%

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Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA

et al. 2017

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Treatment of metastatic colorectal cancer (CRC) has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA), a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool. A tumor-derived fraction of circulating cell-free DNA (cfDNA), isolated from blood samples, may bypass the limitations of currently available biomarkers and could be a tool for noninvasive disease monitoring. Here, total cfDNA levels differentiated a cohort of metastatic CRC patients from healthy controls. Furthermore, we correlated cfDNA during chemotherapy of 27 stage IV patients with clinical parameters to establish its prognostic and predictive value. Indeed, cfDNA levels in chemotherapy naive patients correlate with the tumor burden and CEA values at diagnosis and increase upon disease progression during 1st and 2nd line treatment. Moreover, we confirm the possibility of cfDNA-based genotyping of KRAS to early detect the emergence of resistance during chemotherapy. These data indicate that repetitive quantitative and mutational analysis of cfDNA might complement current treatment standards but may have also limited value in some patients.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA

et al. 2017

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Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

et al. 2019

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Reliable biomarkers are required to evaluate and manage pancreatic ductal adenocarcinoma. Circulating tumor cells and circulating tumor DNA are shed into blood and can be relatively easily obtained from minimally invasive liquid biopsies for serial assays and characterization, thereby providing a unique potential for early diagnosis, forecasting disease prognosis, and monitoring of therapeutic response. In this review, we provide an overview of current technologies used to detect circulating tumor cells and circulating tumor DNA and describe recent advances regarding the multiple clinical applications of liquid biopsy in pancreatic ductal adenocarcinoma.

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Clinical Usefulness of Biological Markers in Pancreatic Cancer

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et al. 2021

Clinical Pancreatology for Practising Gastroenterologists and Surgeons

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Detection of Hot-Spot Mutations in Circulating Cell-Free DNA From Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas

Cited by 78 publications

References 16 publications

Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA

Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

Clinical Usefulness of Biological Markers in Pancreatic Cancer

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