1. Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA
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Maria Zvereva, Gabriel Roberti, Geoffroy Durand, Catherine Voegele, Minh Dao Nguyen, Tiffany M. Delhomme, Priscilia Chopard, Eleonora Fabianova, Zora Adamcakova, Ivana Holcatova, Lenka Foretova, Vladimir Janout, Paul Brennan, Matthieu Foll, Graham B. Byrnes, James D. McKay, Ghislaine Scelo, and Florence Le Calvez-Kelm
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Cell-free DNA ,KRAS mutations ,Plasma ,Pancreatic cancer detection ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: The 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. Methods: We 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. Findings: Higher KRAS amplicon size (167 bp and 218 bp) was associated with lower detectable cell-free DNA mutant allelic fractions (p
- Published
- 2020
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