Plasma-Derived Cell-Free DNA for the Diagnosis of Ocular-Involving Histiocytosis
Year: 2024
Type: article
Study design: Observational Study
Abstract: Purpose Circulating tumor DNA (ctDNA) is released into the plasma by many cancers and offers clinical applications including non-invasive diagnostics. Histiocytosis results from myelogenous clonal expansion of histiocytes, predominantly driven by mutations in the mitogen-activated protein kinase (MAPK) pathway that are potentially detectable by ctDNA-based sequencing assays. However, ocular-involving histiocytosis is often a diagnostic challenge leading to delayed diagnosis and the need for invasive biopsy of sensitive ocular structures. The purpose of this study is to determine whether sequencing of plasma-derived ctDNA can non-invasively diagnose ocular-involving histiocytosis. Participants Twenty-four adult patients with ocular-involving histiocytosis and ctDNA sequencing Design Single tertiary cancer referral center Methods ctDNA was analyzed (via digital droplet PCR for BRAF V600E , and/or next-generation sequencing) and variant allele frequency (VAF) measured at initial presentation to our center. Patient demographics, clinical characteristics, and oncogenic mutations identified from tumor- based sequencing were recorded. Main Outcome Measure Plasma-derived ctDNA detectability of pertinent driver mutations of histiocytosis Results At initial presentation of fourteen patients with ocular-involving histiocytosis, sequencing of plasma-derived ctDNA detected driver mutations for histiocytosis ( BRAF V600E (10), KRAS (2), ARAF (1), and concurrent MAP2K1/KRAS (1)). Mutations found in cfDNA were 100% concordant in 11/11 patients with mutations identified by solid tumor sequencing. Of ten patients without driver mutation detected in ctDNA, 3 patients had alterations ( CBL mutation or kinase fusion) not captured in the ctDNA sequencing assay, 3 were wildtype even by tumor sequencing; and in 4 patients tumor-based sequencing identified mutations ( BRAF (2), MAP2K1 (2)) not detected in ctDNA. Detectable mutations in ctDNA was significantly more likely in patients with uveal infiltration (p = 0.036). Conclusions In this cohort, plasma-derived ctDNA was detectable and diagnostic in the majority of patients with ocular-involving histiocytosis. This suggests that if ocular histiocytosis is suspected (particularly if involving the uvea), noninvasive plasma-derived ctDNA analysis is a helpful diagnostic tool that may obviate the need to invasively biopsy sensitive ocular structures.
Source: Ophthalmology Science
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4394824381