Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA

ZVEREVA, Maria, Gabriel ROBERTI, Geoffroy DURAND, Catherine VOEGELE, Minh Dao Nguyen NGUYEN, Tiffany M. DELHOMME, Priscilia CHOPARD, Eleonora FABIANOVA, Zora ADAMCAKOVA, Ivana HOLCATOVA, Lenka FORETOVÁ, Vladimir JANOUT, Paul BRENNAN, Matthieu FOLL, Graham B. BYRNES, James D. MCKAY, Ghislaine SCELO a Florence LE CALVEZ-KELM. Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA. EBioMedicine. Amsterdam: Elsevier Science BV, roč. 55, MAY 2020, s. 1-8. ISSN 2352-3964. doi:10.1016/j.ebiom.2019.09.042. 2020.

Základní údaje

• Originální název: Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA
• Autoři: ZVEREVA, Maria (643 Rusko), Gabriel ROBERTI (76 Brazílie), Geoffroy DURAND (250 Francie), Catherine VOEGELE (246 Finsko), Minh Dao Nguyen NGUYEN (250 Francie), Tiffany M. DELHOMME (250 Francie), Priscilia CHOPARD (250 Francie), Eleonora FABIANOVA (703 Slovensko), Zora ADAMCAKOVA (703 Slovensko), Ivana HOLCATOVA (203 Česká republika), Lenka FORETOVÁ (203 Česká republika, domácí), Vladimir JANOUT (203 Česká republika), Paul BRENNAN (250 Francie), Matthieu FOLL (250 Francie), Graham B. BYRNES (250 Francie), James D. MCKAY (250 Francie), Ghislaine SCELO (250 Francie) a Florence LE CALVEZ-KELM (250 Francie).
• Vydání: EBioMedicine, Amsterdam, Elsevier Science BV, 2020, 2352-3964.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 30218 General and internal medicine
• Stát vydavatele: Nizozemské království
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 8.143
• Kód RIV: RIV/00216224:14110/20:00116015
• Organizační jednotka: Lékařská fakulta
• Doi: http://dx.doi.org/10.1016/j.ebiom.2019.09.042
• UT WoS: 000537461800001
• Klíčová slova anglicky: Cell-free DNA; KRAS mutations; Plasma; Pancreatic cancer detection
• Štítky: 14110811, rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

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 < 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. Interpretation: Tumour-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. (C) 2019 Published by Elsevier B.V.