Germline Genetic Determinants of Transformation of Uveal Nevi to Melanoma: Towards Early Diagnosis and Prevention of Disease Progression
Abstract
The PI’s research work transformed the field of eye melanoma genetics. Over the last 10 years, the PI provided strong evidence to support contribution of genetics to predisposition to eye melanoma. His work led to the characterization of a new inherited disease caused by mutation in the BAP1 gene that presents with eye melanoma and several other cancers in the patient and bloodline family members. These achievements positions him to be a leader in the fields of uveal melanoma tumor genetics and the BAP1-tumor predisposition syndrome. The focus area of this project is the study of the inherited genetic changes in the subjects that increase the risk for eye melanoma. The proposal addresses the FY20 MRP Challenge statement by redefining eye melanoma disease prevention by identifying subjects at very high risk of their nevi to progress to melanomas. This will allow follow up, and if needed, early intervention, which will ultimately diagnose melanomas at very early stage with excellent outcome of treatment. The proposal will provide a better understanding of the contribution of non-environmental, host risk factors (i.e., genetics) to eye melanoma. The proposed research addresses several of the FY20 MRP Focus Areas including: (i) prevention of melanomagenesis by identifying novel genetic drivers, (ii) computational approaches to address high risk markers, and (iii) therapeutic prevention of eye melanoma by interruption of disease progression. Scientific Objective and Rationale for the Proposed Project: Eye melanoma is a rare but fatal tumor. It is treated by radiation or surgical removal of the eye, leading to loss of vision. Early diagnosis of eye melanoma provides the best outcome in terms of vision and survival. The vast majority of eye melanoma originate in eye nevi, which are common lesions inside the eyes (5%-8% of the population). These nevi are diagnosed by routine non-invasive dilated eye examination. However, given the very low transformation rate to melanoma, early eye melanoma could be missed. The goal of this proposal is to better understand the genetic causes of eye melanoma and develop a biomarker that could be tested in saliva or blood to detect which nevi are at high-risk for progression to melanoma. This allows early treatment if needed. This study will advance the field of cancer research by identifying new genes that, when mutated, increase the risk of the subject and his bloodline family members to cancers. Careful follow-up of these subjects will lead to early diagnosis and improve vision outcome and patients’ survival.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110675
Entities
People
- Mohamed H Abdel-Rahman
Organizations
- Ohio State University
- United States Army