Abstract
Purpose :
There is a paucity of data on the molecular mechanisms driving the local recurrence of uveal melanoma after enucleation, a rare event with devastating consequences. The purpose of this study was to characterize the tumor genetic profile in a patient with local recurrence of uveal melanoma in the intraorbital optic nerve in an anophthalmic orbit seven years after secondary enucleation.
Methods :
Relevant clinical data and MRI imaging were reviewed. Biopsy of the recurrent tumor in the anophthalmic orbit was carried out. Archived primary tumor samples from prior enucleation and biopsy samples of the secondary recurrent tumor were obtained for histopathological analysis. Targeted next-generation sequencing (NGS) of biopsy samples of the secondary recurrent tumor was carried out using the Oncomine (Waltham, MA) Assay Targeted NGS Cancer Gene Panel to evaluate for DNA mutations and/or amplifications in 146 cancer-related genes as well as the presence of gene fusion mRNA transcripts involving 44 oncogenic driver genes.
Results :
Primary tumor samples from the prior enucleation showed a uveal melanoma of mixed spindle and epithelioid cell types without extra-scleral extension or optic nerve invasion. Biopsy of the recurrent tumor showed mixed spindle and epithelioid cell types positive for MelanA and SOX10 on immunohistochemistry, consistent with malignant melanoma. Targeted NGS revealed somatic mutations in GNAQ (Q209L) and the telomerase gene (TERT) promoter (c.1-124C>T). No other mutations were detected in the remaining genes tested including BAP1 and SF3B1.
Conclusions :
This is the first report of an activating TERT promoter mutation in local uveal melanoma recurrence. Future studies on genetic biomarkers in recurrent tumors may lead to rational strategies to reduce the local recurrence of uveal melanoma.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.