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September 16, 2021

Association of Plasma Circulating Tumor DNA With Diagnosis of Metastatic Uveal Melanoma

Author Affiliations
  • 1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Weill-Cornell Medical Center, New York, New York
  • 3Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
  • 4Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
  • 5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Ophthalmol. 2021;139(11):1244-1245. doi:10.1001/jamaophthalmol.2021.3708

Liquid biopsy is a noninvasive means to diagnose, identify targetable mutations, and monitor disease progression, recurrence, and treatment response in cancer. It can be done with circulating tumor cells, microRNAs, exosomes, and cell-free DNA (cfDNA).1 cfDNA can identify specific tumor mutations, referred to as circulating tumor DNA (ctDNA). In uveal melanoma, initiating mutations are mutually exclusive and are recognized as GNAQ, GNA11, CYSLTR2, and PLCB4.1,2 These can be used as a marker of melanocytic tumor origin but not necessarily as signifiers of malignancy, because choroidal nevi also carry these alterations. More pertinent to uveal melanoma and its prognosis are the cooperating driver mutations,1,2 which consist of EIF1AX, SF3B1, and BAP1 in order of increasing potential risk for future metastases. These findings suggest a need for a noninvasive, easily repeatable measure of these driver mutations, one that can circumvent the morbidity of an invasive intraocular procedure and can avoid reliance on a coordinated, anesthetized procedure for specimen retrieval. We report here the potential utility of plasma cfDNA for uveal melanoma: unlike published reports that only interrogate limited exons in initiating mutations,1-3 our assay detects a panel of 129 oncogenes4 including both initiating and mutations driving malignant transformation of uveal melanoma. In our case, the findings suggested that the cfDNA assay potentially heralded the diagnosis of metastatic uveal melanoma, stratified appropriate confirmatory imaging based on the driver mutations, and led to an earlier diagnosis.

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