ArticleEBioMedicine2020
Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 32 citations in OpenAlex.
- Interpretable deep learning model of circulating genomics for quantitative survival prediction in advanced non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Liquid biopsy in gastrointestinal oncology: clinical applications and translational integration of ctDNA, CTCs, and sEVs.Oncology reviews · 2025Review
- Blood-based biomarkers in pancreatic ductal adenocarcinoma: developments over the last decade and what holds for the future- a review.Frontiers in oncology · 2025Review
- Development of a nine-variant reference material panel to standardize cell-free DNA detection.Analytical and bioanalytical chemistry · 2024Article
- Multidimensional fragmentomic profiling of cell-free DNA released from patient-derived organoids.Human genomics · 2023Article
- Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy.International journal of molecular sciences · 2023Article
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- Efficient and accurate KRAS genotyping using digital PCR combined with melting curve analysis for ctDNA from pancreatic cancer patients.Scientific reports · 2023Article
- TP53 mutation detected in circulating exosomal DNA is associated with prognosis of patients with hepatocellular carcinoma.Cancer biology & therapy · 2022Article
- Isolation and Quantification of Plasma Cell-Free DNA Using Different Manual and Automated Methods.Diagnostics (Basel, Switzerland) · 2022Article
- Cancer-cell-derived cell-free DNA can predict distant metastasis earlier in pancreatic cancer: a prospective cohort study.Therapeutic advances in medical oncology · 2022Article
- Measurement Biases Distort Cell-Free DNA Fragmentation Profiles and Define the Sensitivity of Metagenomic Cell-Free DNA Sequencing Assays.Clinical chemistry · 2021Article
- Total and endothelial cell-derived cell-free DNA in blood plasma does not change during menstruation.PloS one · 2021Article
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Authors and funding
18 authors at 6 institutions in 5 countries.
Funding
Abstract
backgroundThe DNA released into the bloodstream by malignant tumours· called circulating tumour DNA (ctDNA), is often a small fraction of total cell-free DNA shed predominantly by hematopoietic cells and is therefore challenging to detect. Understanding the biological properties of ctDNA is key to the investigation of its clinical relevance as a non-invasive marker for cancer detection and monitoring.
methodsWe selected 40 plasma DNA samples of pancreatic cancer cases previously reported to carry a KRAS mutation at the 'hotspot' codon 12 and re-screened the cell-free DNA using a 4-size amplicons strategy (57 bp, 79 bp, 167 bp and 218 bp) combined with ultra-deep sequencing in order to investigate whether amplicon lengths could impact on the capacity of detection of ctDNA, which in turn could provide inference of ctDNA and non-malignant cell-free DNA size distribution.
findingsHigher KRAS amplicon size (167 bp and 218 bp) was associated with lower detectable cell-free DNA mutant allelic fractions (p < 0·0001), with up to 4·6-fold (95% CI: 2·6-8·1) difference on average when comparing the 218bp- and the 57bp-amplicons. The proportion of cases with detectable KRAS mutations was also hampered with increased amplicon lengths, with only half of the cases having detectable ctDNA using the 218 bp assay relative to those detected with amplicons less than 80 bp.
interpretationTumour-derived mutations are carried by shorter cell-free DNA fragments than fragments of wild-type allele. Targeting short amplicons increases the sensitivity of cell-free DNA assays for pancreatic cancer and should be taken into account for optimized assay design and for evaluating their clinical performance.
fundingIARC; MH CZ - DRO; MH SK; exchange program between IARC and Sao Paulo medical Sciences; French Cancer League.
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