Dataset Information

Whole exome profiling and mutational analysis of Ocular Surface Squamous Neoplasia.

ABSTRACT:

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.

SUBMITTER: Ramos-Betancourt N

PROVIDER: S-EPMC7686168 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:There is a trend toward treating conjunctival lesions suspected to be ocular surface squamous neoplasia (OSSN) based on the clinical impression.To describe the presentation of OSSN and identify clinical features that distinguish it from benign lesions and subsequently evaluate their recognizability.Prospective multicenter study in Kenya from July 2012 through July 2014 of 496 adults presenting with conjunctival lesions. One histopathologist examined all specimens. Six additional masked ophthalmologists independently examined photographs from 100 participants and assessed clinical features.Comprehensive history, slitlamp examination, and photography before excision biopsy.Frequency of clinical features in OSSN and benign lesions were recorded. Proportions and means were compared using ?2, Fisher exact test, or t test as appropriate. Interobserver agreement was estimated using the ? statistic. Examiners' assessments were compared with a reference.Among 496 participants, OSSN was the most common (38%) histological diagnosis, followed by pterygium (36%) and actinic keratosis (19%). Patients with OSSN were slightly older (mean [SD] age, 41 [11.6] vs 38 [10.9] years; P?=?.002) and tended to have lower levels of education than patients with benign lesions (P?=?.001). Females predominated (67% of OSSN vs 64% of benign lesions; P?=?.65). Human immunodeficiency virus infection was common among patients with OSSN (74%). The most common location was the nasal limbus (61% OSSN vs 78% benign lesions; P?<?.001). Signs more frequent in OSSN included feeder vessels (odds ratio [OR], 5.8 [95% CI, 3.2-10.5]), moderate inflammation (OR, 3.5 [95% CI, 1.8-6.8]), corneal involvement (OR, 2.7 [95% CI, 1.8-4.0]), leukoplakia (OR, 2.6 [95% CI, 1.7-3.9]), papilliform surface (OR, 2.1 [95% CI, 1.3-3.5]), pigmentation (OR, 1.5 [95% CI, 1.0-2.2]), temporal location (OR, 2.0 [95% CI, 1.2-3.2]), circumlimbal location (6.7% vs 0.3%; P?<?.001), severe inflammation (6.7% vs 0.3%; P?<?.001), and larger mean (SD) diameter (6.8 [3.2] vs 4.8 [2.8] mm; P?<?.001). All OSSN signs were also observed in benign lesions. There was slight to fair interobserver agreement in assessment of most signs and diagnosis (?, 0.1-0.4). The positive predictive value of clinical appearance in identifying OSSN was 54% (interquartile range, 51%-56%) from photographs in which prevalence was 32%.With overlapping phenotypes and modest interobserver agreement, OSSN and benign conjunctival lesions are not reliably distinguished clinically. Point-of-care diagnostic tools may help.