Cardiomyocyte-Specific Circulating Cell-Free Methylated DNA in Esophageal Cancer Patients Treated with Chemoradiation

Autor: Sarah Martinez Roth, Eveline E. Vietsch, Megan E. Barefoot, Marcel O. Schmidt, Matthew D. Park, Archana Ramesh, Michael R. Lindberg, Giuseppe Giaccone, Anna T. Riegel, Ana Barac, Keith Unger, Anton Wellstein
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Gastrointestinal Disorders, Vol 3, Iss 3, Pp 100-112 (2021)
Druh dokumentu: article
ISSN: 2624-5647
DOI: 10.3390/gidisord3030011
Popis: Thoracic high-dose radiation therapy (RT) for cancer has been associated with early and late cardiac toxicity. To assess altered rates of cardiomyocyte cell death due to RT we monitored changes in cardiomyocyte-specific, cell-free methylated DNA (cfDNA) shed into the circulation. Eleven patients with distal esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy (RT) and concurrent carboplatin and paclitaxel were enrolled. Subjects underwent fasting blood draws prior to the initiation and after completion of RT as well as 4–6 months following RT. An island of six unmethylated CpGs in the FAM101A locus was used to identify cardiomyocyte-specific cfDNA in serum. After bisulfite treatment this specific cfDNA was quantified by amplicon sequencing at a depth of >35,000 reads/molecule. Cardiomyocyte-specific cfDNA was detectable before RT in the majority of patient samples and showed some distinct changes during the course of treatment and recovery. We propose that patient-specific cardiac damages in response to the treatment are indicated by these changes although co-morbidities may obscure treatment-specific events.
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