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Abstract
Circulating tumor DNA detection in renal cell carcinoma has long been limited by the disease’s low DNA shedding. An aggressive subtype termed translocation renal cell carcinoma (tRCC) is notably more difficult to detect than the common type, clear-cell RCC, in part due to interindividual variability of gene fusions of the transcription factor TFE3, the driving factor in tRCC. In this issue of the JCI, Garinet et al. reported on an epigenomic liquid biopsy approach that identified a TFE3 fusion–associated chromatin signature specific to tRCC. This work demonstrated that fusion-driven epigenomic alterations can be captured noninvasively and used to distinguish tRCC from other renal cancer subtypes. Beyond its diagnostic potential, the approach described by Garinet et al. may enable disease monitoring and subtype classification in other genetically quiet tumors. Epigenomic liquid biopsy is a promising framework to improve diagnostic accuracy and guide personalized management for tRCC.
Authors
Katsuhiro Ito, David A. Braun
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ISSN: 0021-9738 (print), 1558-8238 (online)