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

Tommaso Grassi, Faye R. Harris, James B. Smadbeck, Stephen J. Murphy, Matthew S. Block, Francesco Multinu, Janet L. Schaefer Klein, Piyan Zhang, Giannoula Karagouga, Minetta C. Liu, Alyssa Larish, Maureen A. Lemens, Marla Kay S. Sommerfield, Serena Cappuccio, John C. Cheville, George Vasmatzis, Andrea Mariani

Research output: Contribution to journalArticlepeer-review


Introduction 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. Methods 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. Results 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. Discussion 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.

Original languageEnglish (US)
Article numbere0252390
JournalPloS one
Issue number6 June
StatePublished - Jun 2021

ASJC Scopus subject areas

  • General


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