Synapse - High-sensitivity mutation analysis of cell-free DNA for disease monitoring in endometrial cancer

High-sensitivity mutation analysis of cell-free DNA for disease monitoring in endometrial cancer Journal Article

Authors:	Ashley, C. W.; Selenica, P.; Patel, J.; Wu, M.; Nincevic, J.; Lakhman, Y.; Zhou, Q.; Shah, R. H.; Berger, M. F.; Da Cruz Paula, A.; Brown, D. N.; Marra, A.; Iasonos, A.; Momeni-Boroujeni, A.; Alektiar, K. M.; Long Roche, K.; Zivanovic, O.; Mueller, J. J.; Zamarin, D.; Broach, V. A.; Sonoda, Y.; Leitao, M. M. Jr; Friedman, C. F.; Jewell, E.; Reis-Filho, J. S.; Ellenson, L. H.; Aghajanian, C.; Abu-Rustum, N. R.; Cadoo, K.; Weigelt, B.
Article Title:	High-sensitivity mutation analysis of cell-free DNA for disease monitoring in endometrial cancer
Abstract:	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 advanced-stage 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 follow-up, 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. See related commentary by Grant et al., p. 305. ©2022 American Association for Cancer Research.
Keywords:	genetics; mutation; endometrial neoplasms; tumor marker; endometrium tumor; procedures; high throughput sequencing; high-throughput nucleotide sequencing; humans; prognosis; human; female; circulating tumor dna; biomarkers, tumor; cell-free nucleic acids; cell free nucleic acid
Journal Title:	Clinical Cancer Research
Volume:	29
Issue:	2
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2023-01-15
Start Page:	410
End Page:	421
Language:	English
DOI:	10.1158/1078-0432.Ccr-22-1134
PUBMED:	36007103
PROVIDER:	scopus
PMCID:	PMC9852004
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146365225&doi=10.1158%2f1078-0432.CCR-22-1134&partnerID=40&md5=041a2e7a4f788fad809f934b1dfab110
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Britta Weigelt -- Source: Scopus