1. Genome Methylation Accurately Predicts Neuroendocrine Tumor Origin: An Online Tool
- Author
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Hackeng, W.M., Dreijerink, K.M.A., Leng, W.W.J. de, Morsink, F.H., Valk, G.D., Vriens, M.R., Offerhaus, G.J.A., Geisenberger, C., Brosens, L.A.A., Hackeng, W.M., Dreijerink, K.M.A., Leng, W.W.J. de, Morsink, F.H., Valk, G.D., Vriens, M.R., Offerhaus, G.J.A., Geisenberger, C., and Brosens, L.A.A.
- Abstract
Item does not contain fulltext, PURPOSE: The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation-based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathologic diagnosis in neuroendocrine tumors. EXPERIMENTAL DESIGN: Methylation data was compiled for 69 small intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (neuroendocrine neoplasm identifier, NEN-ID). The model was validated during 3 × 3 nested cross-validation and tested in a local and an external cohort (n = 198 cases). RESULTS: NEN-ID predicted the origin of tumor samples with high accuracy (>95%). In addition, the diagnostic approach was determined to be robust across a range of possible confounding experimental parameters, such as tumor purity and array quality. A software infrastructure and online user interface were built to make the model available to the scientific community. CONCLUSIONS: This DNA methylation-based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.
- Published
- 2021