Genomic Profiling of Intraocular Leiomyomas Reveals Recurrent Copy Number Alterations

Leiomyomas are benign smooth muscle tumors that commonly present in the uterus, soft tissue, skin, and gastrointestinal tract but in rare cases can also arise within the eye. Notably, intraocular leiomyomas often show slightly different histopathologic and immunohistochemical features, referred to as mesectodermal morphology, given their presumed neural crest origin. Genetic and cytogenetic alterations of intraocular leiomyomas, as well as their association with various clinical and histopathologic features, have not been previously studied.

We identified eight patients diagnosed with intraocular leiomyoma and performed targeted next-generation sequencing, whole transcriptome RNA sequencing, and chromosomal copy number analysis on those with sufficient residual tissue.

Copy number analysis demonstrated multiple, recurrent whole-chromosome losses (including losses of 1, 2, 3, 10, 15q, 22q) suggestive of near haploidization of the genome. DNA sequencing did not reveal any pathogenic single-nucleotide variants, deep deletions, amplifications, or structural rearrangements. Whole-transcriptome RNA sequencing performed in a subset of cases did not show any pathogenic or likely pathogenic gene fusions. Tumors with mesenchymal versus mesectodermal morphology and those with or without histologically worrisome features did not show any differences in their copy number profile.

Genetic and cytogenetic features of intraocular leiomyomas are different from the leiomyomas of uterine and deep soft tissues, as well as from uveal melanocytic tumors.

Recurrent whole-chromosome losses in the absence of mutations or fusions are common among intraocular leiomyomas and may aid in the diagnosis.