High-Sensitivity Mutation Analysis of Cell-Free DNA for Disease Monitoring in Endometrial Cancer

Charles W. Ashley, Pier Selenica, Juber Patel, Wu Michelle, Josip Nincevic, Yulia Lakhman, Qin Zhou, Ronak H. Shah, Michael F. Berger, Arnaud Da Cruz Paula, David N. Brown, Antonio Marra, Alexia Iasonos, Amir Momeni-Boroujeni, Kaled M. Alektiar, Kara Long Roche, Oliver Zivanovic, Jennifer J. Mueller, Dmitriy Zamarin, Vance A. BroachYukio Sonoda, Mario M. Leitao, Claire F. Friedman, Elizabeth Jewell, Jorge S. Reis-Filho, Lora H. Ellenson, Carol Aghajanian, Nadeem R. Abu-Rustum, Karen Cadoo, Britta Weigelt

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Purpose: We sought to determine whether sequencing analysis of circulating cell-free DNA (cfDNA) in patients with prospectively accrued endometrial cancer captures the mutational repertoire of the primary lesion and allows for disease monitoring. Experimental Design: Peripheral blood was prospectively collected from 44 newly diagnosed patients with endometrial cancer over a 24-month period (i.e., baseline, postsurgery, every 6 months after). DNA from the primary endometrial cancers was subjected to targeted next-generation sequencing (NGS) of 468 cancer-related genes, and cfDNA to a high-depth NGS assay of 129 genes with molecular barcoding. Sequencing data were analyzed using validated bioinformatics methods. Results: cfDNA levels correlated with surgical stage in endometrial cancers, with higher levels of cfDNA being present in advancedstage disease. Mutations in cfDNA at baseline were detected preoperatively in 8 of 36 (22%) patients with sequencing data, all of whom were diagnosed with advanced-stage disease, high tumor volume, and/or aggressive histologic type. Of the 38 somatic mutations identified in the primary tumors also present in the cfDNA assay, 35 (92%) and 38 (100%) were detected at baseline and followup, respectively. In 6 patients with recurrent disease, changes in circulating tumor DNA (ctDNA) fraction/variant allele fractions in cfDNA during follow-up closely mirrored disease progression and therapy response, with a lead time over clinically detected recurrence in two cases. The presence of ctDNA at baseline (P < 0.001) or postsurgery (P = 0.014) was significantly associated with reduced progression-free survival. Conclusions: cfDNA sequencing analysis in patients with endometrial cancer at diagnosis has prognostic value, and serial postsurgery cfDNA analysis enables disease and treatment response monitoring.

Original languageEnglish
Pages (from-to)410-421
Number of pages12
JournalClinical Cancer Research
Issue number2
StatePublished - 15 Jan 2023
Externally publishedYes


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