Analysis of Recurrent DNA Base Pair Mismatches in Eye Cancer Patient Genomes

Abstract

Hersh Nanda and Michael T Barrett

This research investigates potential genetic drivers for uveal melanoma (UM), the most frequent primary cancer of the eye, through a frequency and ontology analysis of recurrent genetic mutations in UM patients. Genome data of 32 patients, 23 primary and 9 metastatic, was acquired from the U.S. National Institute of Health (NIH) and obtained from samples that were surgically collected from eye enucleations or resected from liver metastases. It was hypothesized that chromosomes 15 and 16 would predominantly exhibit genetic alterations linked to UM due to their role in the expression of eye color. During analysis, DNA from cancerous tumor cells was compared to a reference DNA sequence (extracted from normal tissue) to identify nucleotide base pair mismatches. The locus of each mutation noted to determine what genes mutated. Pareto analysis of cross-patient data performed to identify chromosomes with the most genetic mutations along with any recurrent genetic mutations across patients. A gene ontology (GO) analysis conducted to study the functions of mutated genes and investigate possible links to cancer, such as anomalies in genes with a known role in tumor suppression. A total of 130 genetic mutations were identified (7 recurrent and 123 non-recurrent), with most mutations occurring in chromosomes 3 and X. Recurrent mutations varied from 8.7% to 17.39% occurrence in the UM patient sample. The recurring mutations observed as missense mutations in seven genes. These findings suggest that UM is a recessive heterogeneous disease with selected homozygous mutations. Notably, this study has potential wider significance because the seven genes targeted by recurrent mutations affected in other cancers. It concluded that immunotherapy is a highly promising treatment for Uveal Melanoma due to the disease’s heterogeneous nature.

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