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

J 2020

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 et. al.

Basic information

Original name

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

Authors

ZVEREVA, Maria (643 Russian Federation), Gabriel ROBERTI (76 Brazil), Geoffroy DURAND (250 France), Catherine VOEGELE (246 Finland), Minh Dao Nguyen NGUYEN (250 France), Tiffany M. DELHOMME (250 France), Priscilia CHOPARD (250 France), Eleonora FABIANOVA (703 Slovakia), Zora ADAMCAKOVA (703 Slovakia), Ivana HOLCATOVA (203 Czech Republic), Lenka FORETOVÁ (203 Czech Republic, belonging to the institution), Vladimir JANOUT (203 Czech Republic), Paul BRENNAN (250 France), Matthieu FOLL (250 France), Graham B. BYRNES (250 France), James D. MCKAY (250 France), Ghislaine SCELO (250 France) and Florence LE CALVEZ-KELM (250 France)

Edition

EBioMedicine, Amsterdam, Elsevier Science BV, 2020, 2352-3964

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30218 General and internal medicine

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.143

RIV identification code

RIV/00216224:14110/20:00116015

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.ebiom.2019.09.042

UT WoS

000537461800001

Keywords in English

Cell-free DNA; KRAS mutations; Plasma; Pancreatic cancer detection

Abstract

V originále

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.

Citovat

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 and 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, 2020, vol. 55, MAY 2020, p. 1-8. ISSN 2352-3964. Available from: https://dx.doi.org/10.1016/j.ebiom.2019.09.042.

@article{1670505,
   author = {Zvereva, Maria and Roberti, Gabriel and Durand, Geoffroy and Voegele, Catherine and Nguyen, Minh Dao Nguyen and Delhomme, Tiffany M. and Chopard, Priscilia and Fabianova, Eleonora and Adamcakova, Zora and Holcatova, Ivana and Foretová, Lenka and Janout, Vladimir and Brennan, Paul and Foll, Matthieu and Byrnes, Graham B. and McKay, James D. and Scelo, Ghislaine and Le CalvezandKelm, Florence},
   article_location = {Amsterdam},
   article_number = {MAY 2020},
   doi = {http://dx.doi.org/10.1016/j.ebiom.2019.09.042},
   keywords = {Cell-free DNA; KRAS mutations; Plasma; Pancreatic cancer detection},
   language = {eng},
   issn = {2352-3964},
   journal = {EBioMedicine},
   title = {Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA},
   url = {https://www.sciencedirect.com/science/article/pii/S2352396419306462?via%3Dihub},
   volume = {55},
   year = {2020}
}

TY  - JOUR
ID  - 1670505
AU  - Zvereva, Maria - Roberti, Gabriel - Durand, Geoffroy - Voegele, Catherine - Nguyen, Minh Dao Nguyen - Delhomme, Tiffany M. - Chopard, Priscilia - Fabianova, Eleonora - Adamcakova, Zora - Holcatova, Ivana - Foretová, Lenka - Janout, Vladimir - Brennan, Paul - Foll, Matthieu - Byrnes, Graham B. - McKay, James D. - Scelo, Ghislaine - Le Calvez-Kelm, Florence
PY  - 2020
TI  - Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA
JF  - EBioMedicine
VL  - 55
IS  - MAY 2020
SP  - 1-8
EP  - 1-8
PB  - Elsevier Science BV
SN  - 23523964
KW  - Cell-free DNA
KW  - KRAS mutations
KW  - Plasma
KW  - Pancreatic cancer detection
UR  - https://www.sciencedirect.com/science/article/pii/S2352396419306462?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S2352396419306462?via%3Dihub
N2  - 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.
ER  -

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 and Florence LE CALVEZ-KELM. Circulating tumour-derived KRAS mutations in pancreatic cancer cases are predominantly carried by very short fragments of cell-free DNA. \textit{EBioMedicine}. Amsterdam: Elsevier Science BV, 2020, vol.~55, MAY 2020, p.~1-8. ISSN~2352-3964. Available from: https://dx.doi.org/10.1016/j.ebiom.2019.09.042.

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