Treatment response monitoring in patients with advanced malignancies using cell-free SHOX2 and SEPT9 DNA methylation in blood: An observational prospective study.
The Journal of Molecular Diagnostics 2020 April 30 [Link]
de Vos L, Jung M, Koerber RM, Bawden EG, Holderried TAW, Dietrich J, Bootz F, Brossart P, Kristiansen G, Dietrich D
Patients with incurable cancer usually receive palliative treatment with significant toxicity and limited efficacy. Methylation analysis of circulating cell-free DNA in blood from cancer patients represents a promising approach for minimally invasive, real-time monitoring of treatment response. SHOX2 and SEPT9 methylation was analyzed in N=8,865 malignant and N=746 normal adjacent tissues across 33 different malignancies from The Cancer Genome Atlas. Furthermore, we performed quantitative SHOX2 and SEPT9 circulating cell-free DNA methylation analysis in plasma obtained before and consecutively during treatment from prospectively enrolled N=115 patients with various advanced cancers. SHOX2 and/or SEPT9 hypermethylation in malignant tissues is present in various carcinomas, sarcoma, melanoma, brain tumors, mesothelioma, and hematopoietic malignancies. Among the prospectively enrolled cancer patients, 61% (70/115) of patients had a baseline-positive blood cumulative ccfDNA methylation score (CMS) and were eligible for response monitoring. Dynamic changes of CMS during treatment were strongly associated with treatment response. An CMS increase indicated change up to 80 days prior to conventional monitoring. SHOX2 and SEPT9 circulating cell-free DNA methylation represents a pan-cancer biomarker and has the potential to be a powerful tool for monitoring treatment response in patients with solid tumors and lymphomas. The early identification of non-responders might allow for a timely change of treatment regimen.