Whole Exome Profiling and Mutational Analysis of Ocular Surface Squamous Neoplasia

Abstract

Purpose : To perform whole exome profiling and mutational analysis of 10 patients with diagnosis of Ocular Surface Squamous Neoplasia (OSSN).

Methods : Ten patients were prospectively recruited from Cornea and Refractive Surgery Department at Asociación para Evitar la Ceguera en México, from April to September 2017. This study had Institutional Review Board approval and informed consent was obtained from all patients. Inclusion criteria were patients with clinical suspicion of OSSN, older than 18 years, with typical signs of OSSN by HR-OCT.
Incisional biopsies were performed on all subjects. After histopathology confirmation and grading of OSSN, whole exome sequencing analysis was conducted in the Sequencing Core facility at the University of Miami as previously published by Wang G. et al. Mutational analysis was conducted and further filtered for oncogenic driver genes and mutations.

Results : Mean age of patients was 69 years, 60% were men. All patients were identified as Mexican mestizo. On histopathologic examination, 3 cases were mild dysplasia, 3 moderate dysplasia, and 4 cases were carcinoma in situ.
Since over 9000 mutations were found in exome analysis amongst the samples, a recently published Comprehensive characterization of driver genes and mutations dataset was used to filter our data for known oncogenic driver mutations, obtaining approximately 320 mutations.
All samples carried at least one mutation in a DNA repair and cell cycle gene. Five OSSN samples carry mutations in TP53. Mutations in MSH6 were identified in 4 samples and five samples carry mutations in BRCA1/2. Other mutations identified were ATM, ATR, ATRX, MSH2, POLQ, CHEK2, SMC1A, ABL1, PMS1, ERCC2, MTOR, MSH3, RB1 and CDKN2A.
Most of the samples (9 out of 10) also carried a mutation in a development and growth pathway. The most frequent mutation, in five samples was HGF. Four OSSN samples carry mutations in APC; four samples carry mutations in PDGRFRA; and four in PTCH1. Other mutations identified were NOTCH1/2, TCF7L2, ERBB2/3/4, and AXIN1/2.

Conclusions : All samples carried at least one mutation in a DNA repair and cell cycle gene, and most of the samples also carried a mutation in a development and growth pathway.
There were some overlapping genes with the original published dataset, such as ERBB4, SETD2, KIT and RB1, but the mutation profiles of these 10 samples were remarkably different from the previously published cases.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.