Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer

KRAS mutation is a major regulator in the tumor progression of pancreatic cancer. Here, we compared the frequency and mutation burden of KRAS mutation subtypes with paired tumor tissue and blood in patients and examined their clinical significance. DNA from tumor tissues and cell-free DNA (cfDNA) fr...

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Autores principales:	Eunsung Jun, Bonhan Koo, Eo Jin Kim, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Woohyung Lee, Yejong Park, Sarang Hong, Yong Shin, Song Cheol Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pancreatic cancer cell-free DNA KRAS mutation G12D G12V mutation burden Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8107464f28654abc942af90be613bfaf
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spelling	oai:doaj.org-article:8107464f28654abc942af90be613bfaf2021-11-25T16:49:28ZAnalysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer10.3390/biomedicines91115992227-9059https://doaj.org/article/8107464f28654abc942af90be613bfaf2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1599https://doaj.org/toc/2227-9059KRAS mutation is a major regulator in the tumor progression of pancreatic cancer. Here, we compared the frequency and mutation burden of KRAS mutation subtypes with paired tumor tissue and blood in patients and examined their clinical significance. DNA from tumor tissues and cell-free DNA (cfDNA) from preoperative blood were obtained from 70 patients with pancreatic cancer. Subtypes and mutation burdens of KRAS G12D and G12V mutations were evaluated using droplet digital PCR. Comparing the presence of mutations in tissue, accumulative and simultaneous mutations of G12D or G12V were identified of 67 (95.7%), and 48 patients (68.6%). Conversely, in blood, they were only identified in 18 (25.7%) and four (5.7%) patients; respectively. Next, comparing the mutation burden in tissue, the mutation burden varied from less than 0.1 to more than five, whereas that of cfDNA in blood was mostly between one and five, as cases with a mutation burden lower than 0.1 and higher than five were rare. Finally, the presence of the G12V mutation alone in cfDNA and the combination of the G12V mutation with elevated CA 19-9 levels were associated with poor recurrence-free survival. These fundamental data on the KRAS mutation subtypes and their clinical significance could support their potential as predictive markers for postoperative recurrence.Eunsung JunBonhan KooEo Jin KimDae Wook HwangJae Hoon LeeKi Byung SongWoohyung LeeYejong ParkSarang HongYong ShinSong Cheol KimMDPI AGarticlepancreatic cancercell-free DNAKRAS mutationG12DG12Vmutation burdenBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1599, p 1599 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic cancer cell-free DNA KRAS mutation G12D G12V mutation burden Biology (General) QH301-705.5
spellingShingle	pancreatic cancer cell-free DNA KRAS mutation G12D G12V mutation burden Biology (General) QH301-705.5 Eunsung Jun Bonhan Koo Eo Jin Kim Dae Wook Hwang Jae Hoon Lee Ki Byung Song Woohyung Lee Yejong Park Sarang Hong Yong Shin Song Cheol Kim Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer
description	KRAS mutation is a major regulator in the tumor progression of pancreatic cancer. Here, we compared the frequency and mutation burden of KRAS mutation subtypes with paired tumor tissue and blood in patients and examined their clinical significance. DNA from tumor tissues and cell-free DNA (cfDNA) from preoperative blood were obtained from 70 patients with pancreatic cancer. Subtypes and mutation burdens of KRAS G12D and G12V mutations were evaluated using droplet digital PCR. Comparing the presence of mutations in tissue, accumulative and simultaneous mutations of G12D or G12V were identified of 67 (95.7%), and 48 patients (68.6%). Conversely, in blood, they were only identified in 18 (25.7%) and four (5.7%) patients; respectively. Next, comparing the mutation burden in tissue, the mutation burden varied from less than 0.1 to more than five, whereas that of cfDNA in blood was mostly between one and five, as cases with a mutation burden lower than 0.1 and higher than five were rare. Finally, the presence of the G12V mutation alone in cfDNA and the combination of the G12V mutation with elevated CA 19-9 levels were associated with poor recurrence-free survival. These fundamental data on the KRAS mutation subtypes and their clinical significance could support their potential as predictive markers for postoperative recurrence.
format	article
author	Eunsung Jun Bonhan Koo Eo Jin Kim Dae Wook Hwang Jae Hoon Lee Ki Byung Song Woohyung Lee Yejong Park Sarang Hong Yong Shin Song Cheol Kim
author_facet	Eunsung Jun Bonhan Koo Eo Jin Kim Dae Wook Hwang Jae Hoon Lee Ki Byung Song Woohyung Lee Yejong Park Sarang Hong Yong Shin Song Cheol Kim
author_sort	Eunsung Jun
title	Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer
title_short	Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer
title_full	Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer
title_fullStr	Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer
title_full_unstemmed	Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer
title_sort	analysis of kras mutation subtype in tissue dna and cell-free dna using droplet digital pcr and the function of cell-free dna as a recurrence predictive marker in pancreatic cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8107464f28654abc942af90be613bfaf
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Analysis of KRAS Mutation Subtype in Tissue DNA and Cell-Free DNA Using Droplet Digital PCR and the Function of Cell-Free DNA as a Recurrence Predictive Marker in Pancreatic Cancer

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