TERT promoter mutated circulating tumor DNA as a biomarker for prognosis in hepatocellular carcinoma

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TERT promoter mutated circulating tumor DNA as a biomarker for prognosis in hepatocellular carcinoma. / Oversoe, Stine K; Clement, Michelle S; Pedersen, Michael H; Weber, Britta; Aagaard, Niels Kristian; Villadsen, Gerda E; Grønbæk, Henning; Hamilton-Dutoit, Stephen J; Sorensen, Boe S; Kelsen, Jens.

In: Scandinavian Journal of Gastroenterology, Vol. 55, No. 12, 12.2020, p. 1433-1440.

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@article{90abcded3ce440fdb2ac7947e102ab54,
title = "TERT promoter mutated circulating tumor DNA as a biomarker for prognosis in hepatocellular carcinoma",
abstract = "BACKGROUND AND AIMS: Plasma circulating tumor DNA (ctDNA) with tumor-specific mutations is an attractive biomarker. The telomerase reverse transcriptase (TERT) C228T promoter mutation is the most prevalent tumor-associated mutation in hepatocellular carcinoma (HCC). We evaluated the presence and prognostic value of the TERT C228T mutation in plasma and tissue in a Danish HCC cohort.METHODS: We analyzed ctDNA from 95 HCC patients and 45 liver cirrhotic patients without HCC for the TERT mutation using droplet digital polymerase chain reaction. We also analyzed DNA from the corresponding primary tumor tissues in 34 HCC patients.RESULTS: The plasma TERT C228T mutation was detected in 42/95 HCC patients (44%) but in none of the non-HCC patients. The TERT mutation was detected in 23/34 tumor samples (68%). The TERT mutation was associated with increased mortality when detected in plasma (adjusted HR 2.16 (1.20-3.88), p = .010) but not in tumor tissue (adjusted HR 1.11 (0.35-3.56), p = .860). There was a positive correlation between the presence of the TERT mutation in plasma and an advanced TNM stage (p < .0001) and vascular invasion (p = .005). Analysis of the TERT mutation in plasma and tumor DNA from the same patient was concordant in 21/34 samples (62%; kappa value 0.31, p = .014). Non-concordance was associated with an early TNM stage.CONCLUSION: The plasma TERT mutation was detected in 44% of HCC patients and in none of non-HCC cirrhotic patients; and was associated with increased mortality. We propose the TERT C228T mutation in ctDNA as a promising HCC biomarker for prognosis.",
keywords = "Hepatobiliary-clinical, cancer genomics, circulating tumor DNA, droplet digital PCR, hepatocellular carcinoma, oncology-clinical",
author = "Oversoe, {Stine K} and Clement, {Michelle S} and Pedersen, {Michael H} and Britta Weber and Aagaard, {Niels Kristian} and Villadsen, {Gerda E} and Henning Gr{\o}nb{\ae}k and Hamilton-Dutoit, {Stephen J} and Sorensen, {Boe S} and Jens Kelsen",
year = "2020",
month = dec,
doi = "10.1080/00365521.2020.1837928",
language = "English",
volume = "55",
pages = "1433--1440",
journal = "Scandinavian Journal of Gastroenterology",
issn = "0036-5521",
publisher = "Taylor & Francis ",
number = "12",

}

RIS

TY - JOUR

T1 - TERT promoter mutated circulating tumor DNA as a biomarker for prognosis in hepatocellular carcinoma

AU - Oversoe, Stine K

AU - Clement, Michelle S

AU - Pedersen, Michael H

AU - Weber, Britta

AU - Aagaard, Niels Kristian

AU - Villadsen, Gerda E

AU - Grønbæk, Henning

AU - Hamilton-Dutoit, Stephen J

AU - Sorensen, Boe S

AU - Kelsen, Jens

PY - 2020/12

Y1 - 2020/12

N2 - BACKGROUND AND AIMS: Plasma circulating tumor DNA (ctDNA) with tumor-specific mutations is an attractive biomarker. The telomerase reverse transcriptase (TERT) C228T promoter mutation is the most prevalent tumor-associated mutation in hepatocellular carcinoma (HCC). We evaluated the presence and prognostic value of the TERT C228T mutation in plasma and tissue in a Danish HCC cohort.METHODS: We analyzed ctDNA from 95 HCC patients and 45 liver cirrhotic patients without HCC for the TERT mutation using droplet digital polymerase chain reaction. We also analyzed DNA from the corresponding primary tumor tissues in 34 HCC patients.RESULTS: The plasma TERT C228T mutation was detected in 42/95 HCC patients (44%) but in none of the non-HCC patients. The TERT mutation was detected in 23/34 tumor samples (68%). The TERT mutation was associated with increased mortality when detected in plasma (adjusted HR 2.16 (1.20-3.88), p = .010) but not in tumor tissue (adjusted HR 1.11 (0.35-3.56), p = .860). There was a positive correlation between the presence of the TERT mutation in plasma and an advanced TNM stage (p < .0001) and vascular invasion (p = .005). Analysis of the TERT mutation in plasma and tumor DNA from the same patient was concordant in 21/34 samples (62%; kappa value 0.31, p = .014). Non-concordance was associated with an early TNM stage.CONCLUSION: The plasma TERT mutation was detected in 44% of HCC patients and in none of non-HCC cirrhotic patients; and was associated with increased mortality. We propose the TERT C228T mutation in ctDNA as a promising HCC biomarker for prognosis.

AB - BACKGROUND AND AIMS: Plasma circulating tumor DNA (ctDNA) with tumor-specific mutations is an attractive biomarker. The telomerase reverse transcriptase (TERT) C228T promoter mutation is the most prevalent tumor-associated mutation in hepatocellular carcinoma (HCC). We evaluated the presence and prognostic value of the TERT C228T mutation in plasma and tissue in a Danish HCC cohort.METHODS: We analyzed ctDNA from 95 HCC patients and 45 liver cirrhotic patients without HCC for the TERT mutation using droplet digital polymerase chain reaction. We also analyzed DNA from the corresponding primary tumor tissues in 34 HCC patients.RESULTS: The plasma TERT C228T mutation was detected in 42/95 HCC patients (44%) but in none of the non-HCC patients. The TERT mutation was detected in 23/34 tumor samples (68%). The TERT mutation was associated with increased mortality when detected in plasma (adjusted HR 2.16 (1.20-3.88), p = .010) but not in tumor tissue (adjusted HR 1.11 (0.35-3.56), p = .860). There was a positive correlation between the presence of the TERT mutation in plasma and an advanced TNM stage (p < .0001) and vascular invasion (p = .005). Analysis of the TERT mutation in plasma and tumor DNA from the same patient was concordant in 21/34 samples (62%; kappa value 0.31, p = .014). Non-concordance was associated with an early TNM stage.CONCLUSION: The plasma TERT mutation was detected in 44% of HCC patients and in none of non-HCC cirrhotic patients; and was associated with increased mortality. We propose the TERT C228T mutation in ctDNA as a promising HCC biomarker for prognosis.

KW - Hepatobiliary-clinical

KW - cancer genomics

KW - circulating tumor DNA

KW - droplet digital PCR

KW - hepatocellular carcinoma

KW - oncology-clinical

UR - http://www.scopus.com/inward/record.url?scp=85094130631&partnerID=8YFLogxK

U2 - 10.1080/00365521.2020.1837928

DO - 10.1080/00365521.2020.1837928

M3 - Journal article

C2 - 33103505

VL - 55

SP - 1433

EP - 1440

JO - Scandinavian Journal of Gastroenterology

JF - Scandinavian Journal of Gastroenterology

SN - 0036-5521

IS - 12

ER -