Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression

Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitor...

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Main Authors: Esther L. Moss, Diviya N. Gorsia, Anna Collins, Pavandeep Sandhu, Nalini Foreman, Anupama Gore, Joey Wood, Christopher Kent, Lee Silcock, David S. Guttery
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/8/2231
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spelling doaj-dd041299a3b8434da37d91cbd64be3fe2020-11-25T03:25:45ZengMDPI AGCancers2072-66942020-08-01122231223110.3390/cancers12082231Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and ProgressionEsther L. Moss0Diviya N. Gorsia1Anna Collins2Pavandeep Sandhu3Nalini Foreman4Anupama Gore5Joey Wood6Christopher Kent7Lee Silcock8David S. Guttery9Leicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester LE2 7LX, UKLeicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester LE2 7LX, UKLeicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester LE2 7LX, UKLeicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester LE2 7LX, UKLeicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester LE2 7LX, UKDepartment of Gynaecological Oncology, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester LE5 4PW, UKDepartment of Gynaecological Oncology, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester LE5 4PW, UKDepartment of Gynaecological Oncology, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester LE5 4PW, UKNonacus Limited, Birmingham Research Park, Birmingham B15 2SQ, UKLeicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester LE2 7LX, UKDespite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.https://www.mdpi.com/2072-6694/12/8/2231endometrial cancercirculating tumor DNAdigital droplet PCRion torrentwhole exome sequencing
collection DOAJ
language English
format Article
sources DOAJ
author Esther L. Moss
Diviya N. Gorsia
Anna Collins
Pavandeep Sandhu
Nalini Foreman
Anupama Gore
Joey Wood
Christopher Kent
Lee Silcock
David S. Guttery
spellingShingle Esther L. Moss
Diviya N. Gorsia
Anna Collins
Pavandeep Sandhu
Nalini Foreman
Anupama Gore
Joey Wood
Christopher Kent
Lee Silcock
David S. Guttery
Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression
Cancers
endometrial cancer
circulating tumor DNA
digital droplet PCR
ion torrent
whole exome sequencing
author_facet Esther L. Moss
Diviya N. Gorsia
Anna Collins
Pavandeep Sandhu
Nalini Foreman
Anupama Gore
Joey Wood
Christopher Kent
Lee Silcock
David S. Guttery
author_sort Esther L. Moss
title Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression
title_short Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression
title_full Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression
title_fullStr Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression
title_full_unstemmed Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression
title_sort utility of circulating tumor dna for detection and monitoring of endometrial cancer recurrence and progression
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2020-08-01
description Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.
topic endometrial cancer
circulating tumor DNA
digital droplet PCR
ion torrent
whole exome sequencing
url https://www.mdpi.com/2072-6694/12/8/2231
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