Personalized tumor-specific DNA junctions to detect circulating tumor in patients with endometrial cancer

There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot s...

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Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0252390
Main Authors: Grassi, Tommaso, Harris, Faye R, Smadbeck, James B, Murphy, Stephen J, Block, Matthew S, Multinu, Francesco, Schaefer Klein, Janet L, Zhang, Piyan, Karagouga, Giannoula, Liu, Minetta C, Larish, Alyssa, Lemens, Maureen A, Sommerfield, Marla Kay S, Cappuccio, Serena, Cheville, John C, Vasmatzis, George, Mariani, Andrea
Format: Article
Language:English
Subjects:
Analysis
Biology and life sciences
Biomarkers
Breast cancer
Cancer therapies
Circulating Tumor DNA - blood
Data analysis
Deoxyribonucleic acid
DNA
Editing
Endometrial cancer
Endometrial Neoplasms - blood
Endometrial Neoplasms - diagnosis
Endometrial Neoplasms - pathology
Endometrium
Female
Funding
Genetic aspects
Genomes
Gynecology
Humans
Lymph nodes
Lymphatic system
Medicine
Medicine and Health Sciences
Methodology
Mutation
Obstetrics
Oncology
Ovarian cancer
Patients
Plasma
Precision Medicine
Research and Analysis Methods
Research ethics
Surgery
Tumors
Uterine cancer
Uterus
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Summary:There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot study, we investigated if unique tumor-specific DNA junctions can be used to detect ctDNA levels in patients with endometrial cancer. Chromosomal rearrangements in primary tumors of eleven patients with high-grade or advanced stage endometrial cancer were determined by whole-genome Mate-Pair sequencing. Identified unique tumor-specific junctions were evaluated in pre- and six-week post-surgery patient plasma using individualized quantitative polymerase chain reaction (qPCR) assays. The relationship between clinicopathological features and detection of ctDNA was investigated. CtDNA was detected in 60% (6/10) of cases pre-surgery and in 27% (3/11) post-surgery. The detection of ctDNA pre-surgery was consistent with clinical indicators of aggressive disease such as advanced stage (80% - 4/5), lymphatic spread of disease (100% - 3/3), serous histology (80% - 4/5), deep myometrial invasion (100% - 3/3), lympho-vascular space invasion (75% - 3/4). All patients in which ctDNA was detected post-surgically had type II endometrial cancer. This pilot study demonstrates the feasibility of using personalized tumor-specific junction panels for detecting ctDNA in the plasma of endometrial cancer patients. Larger studies and longer follow-up are needed to validate the potential association between pre-surgical ctDNA detection and the presence of cancers with aggressive pathologic tumor characteristics or advanced stage observed in this study.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0252390