Oncologist-led germline genetic testing for uveal melanoma

Area of Science:

• Oncology
• Genetics
• Ophthalmology

Background:

• Uveal melanoma (UM) is the most common primary intraocular malignancy.
• Germline mutations, particularly in the BAP1 gene, are implicated in hereditary cancer predisposition syndromes.
• Genetic testing plays a crucial role in identifying individuals at risk for hereditary cancers.

Purpose of the Study:

• To determine the genotype and phenotype of unselected uveal melanoma (UM) patients undergoing germline multi-gene panel genetic testing.
• To evaluate the role of a medical genetics clinic in a mainstreaming model for genetic testing and counselling in UM patients.
• To identify the prevalence of germline BAP1 mutations in a cohort of unselected UM patients.

Main Methods:

• Retrospective chart review of clinical and genetic data from UM patients who underwent germline genetic testing (December 2019 - October 2021).
• Multi-gene panel analysis of extracted DNA from peripheral blood samples, including genes associated with hereditary melanoma.
• Statistical analysis to evaluate correlations between genotype (BAP1 status) and phenotype (family history, metastatic disease).

Main Results:

• A pathogenic BAP1 variant was identified in 3.5% (4/114) of unselected UM patients.
• Germline BAP1 mutation status was significantly associated with a family history of mesothelioma (p=0.0015) and metastatic disease (p=0.017).
• No other significant associations were found between patient/tumor characteristics and germline BAP1 results.

Conclusions:

• Germline BAP1 mutations are present in a subset of unselected UM patients.
• An oncologist-initiated, genetics-led mainstreaming model facilitates genetic testing and counselling for UM patients.
• This model is effective for identifying hereditary cancer predisposition in UM patients and streamlining cancer screening.