Fig. 3

Longitudinal methylation profiles of patient-derived cfDNA in other malignancies. A Assessing tumor burden in patient P4822 with metastatic pancreatic neuroendocrine carcinoma. The overall cfDNA sequencing yield (top) is plotted against the number of reads with methylation profiles matching the primary tumor with a tumor score of > 0.9 (bottom). Clinically relevant events are annotated. Clinically relevant events are annotated. Everolimus and peptide receptor radionuclide therapy (PRRT) was used for treatment of the metastatic neuroendocrine cancer. Positron-emission tomography (PET) was combined with CT imaging. B Longitudinal gene-level analysis of cfDNA changes in P4822. The number of tumor-specific differentially methylated genes found to be matching in cfDNA is shown for each time point. Differentially methylated genes were identified as those with the largest difference in methylation between the primary tumor and immune cells. Such methylated genes observed in cfDNA are defined as matching the primary tumor when its methylation state (e.g., hypermethylation or hypomethylation) is concordant. Specific time points are annotated with asterisks to denote clinical events with significant changes in methylation. C Assessing tumor burden in patient P6527 with metastatic cholangiocarcinoma. The overall cfDNA sequencing yield (top) is plotted against the number of reads with methylation profiles matching the primary tumor with a tumor score of > 0.9 (bottom). Clinically relevant events are annotated. Treatment included gemcitabine and a chemotherapy combination of 5-fluouracil and oxaliplatin (FOLFOX) was used for treatment of the cholangiocarcinoma. D Longitudinal gene-level analysis of cfDNA changes in P6527. The number of tumor-specific differentially methylated genes found to be matching in cfDNA is shown for each time point. Differentially methylated genes were identified as those with the largest difference in methylation between the primary tumor and immune cells. Such methylated genes observed in cfDNA are defined as matching the primary tumor when its methylation state (e.g., hypermethylation or hypomethylation) is concordant. Specific time points are annotated with asterisks to denote clinical events with significant changes in methylation