Whole exome profiling and mutational analysis of Ocular Surface Squamous Neoplasia

Nallely Ramos-Betancourt, Matthew G. Field, Jesus H. Davila-Alquisiras, Carol L. Karp, Luis F. Hernández-Zimbrón, Roberto García-Vázquez, Kristian A. Vazquez-Romo, Gaofeng Wang, Jans Fromow-Guerra, Everardo Hernandez-Quintela, Anat Galor

Research output: Contribution to journalArticlepeer-review


Purpose: To determine genetic mutational profiles in patients with Ocular Surface Squamous Neoplasia (OSSN) using whole exome sequencing. Methods: Prospective, case-series study. Patient recruitment was conducted in a single tertiary referral center from April to September 2017. Specimens were obtained by incisional biopsies of tumors from ten eyes with histopathologic confirmation of OSSN. DNA whole exome sequencing and mutation analysis were performed. Results: Ten patients with clinically-diagnosed OSSN underwent DNA whole exome sequencing analysis. Deleterious mutations in 305 genes known to drive tumor development and progression were found. These mutations centered around two main pathways: DNA repair/cell cycle and development/growth. All ten samples had at least one mutation in a DNA repair/cell cycle gene and all but one sample had one in a development/growth gene. The most common mutation was found in TP53 and HGF (both present in 50% of cases) and mutually exclusive mutations were found in BRCA1 and BRCA2 (50% of cases). Mutations in APC, MSH6, PDGFRA, and PTCH1 were found in 40% of cases. Global mutation analysis identified ultraviolet induced radiation as the only mutational signature present in the dataset. Conclusions: Mutations found in samples from patients with OSSN are mainly induced by ultraviolet radiation and occur within two main pathways related to DNA repair/cell cycle and development/growth. There are many clinically available drugs and several others being evaluated in clinical trials that target the genes found mutated in this study, offering new therapeutic options for OSSN.

Original languageEnglish (US)
Pages (from-to)627-632
Number of pages6
JournalOcular Surface
Issue number4
StatePublished - Oct 2020


  • Mutational analysis
  • Ocular Surface Squamous Neoplasia
  • Whole exome sequencing

ASJC Scopus subject areas

  • Ophthalmology


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