Oncologist-led germline genetic testing for uveal melanoma

ABSTRACT

Purpose

To report the genotype and phenotype of a cohort of unselected uveal melanoma (UM) patients who had germline multi-gene panel genetic testing, including the BAP1 gene, from a large multi-ethnic cancer centre. We describe the central role of the medical genetics clinic in collaboration with oncologists in a mainstreaming model to facilitate genetic testing, counselling and streamlining of patients with hereditary cancer predisposition.

Methods

A retrospective chart review of clinical and genetic findings of unselected UM patients who had germline genetic testing between December 2019 and October 2021 was conducted. Extracted DNA from peripheral blood samples were analyzed with a multi-gene panel that included at least six genes associated with hereditary melanoma. The correlation between the genotype and the phenotype of the cohort was evaluated. Statistical analysis comprised descriptive and comparative statistics with significance assigned at p < .05. The genetics clinic streamlined patients among the relevant oncology clinics for cancer screening in germline BAP1 positive individuals.

Results

In unselected UM patients, 3.5% (4/114) tested positive for a BAP1 pathogenic variant. Germline BAP1 status was associated with a family history of mesothelioma (p = .0015) and metastatic disease (p = .017). There were no other significant associations between the patient- or tumour-related characteristics and germline BAP1 results.

Conclusion

A germline BAP1 mutation was detected in 3.5% of unselected UM patients. The oncologist-initiated and genetics-led mainstreaming model is a straightforward process and can be utilized for offering genetic testing to all UM patients.

KEYWORDS:

• Uveal melanoma
• hereditary cancer
• BAP1
• mainstreaming
• genetic counselling
• service delivery

Acknowledgments

The authors thank Dr. Osvaldo Espin-Garcia for statistical analysis. This work was also made possible thanks to the Bhalwani Family Charitable Fund and The Princess Margaret Foundation.

Author contributions

Brittany Gillies: Conceptualization, data curation, formal analysis, investigation, methodology, project administration, visualization, writing (original draft, review, editing). Hatem Krema: Conceptualization, methodology, resources, supervision, writing (original draft, review, editing). Anning Chao: data curation, investigation, resources. Leonardo Lando: data curation, formal analysis, investigation, resources, writing (review, editing). Kirsten Farncombe: project administration, supervision, writing (review, editing). Marcus Butler: Conceptualization, resources. Filiberto Altomare: Conceptualization, resources. Raymond H. Kim: Conceptualization, funding acquisition, methodology, supervision, writing (review, editing).

Disclosure statement

R.H.K is supported by the Bhalwani Family Charitable Fund, FDC Foundation, Karen Green and George Fischer Genomics and Genetics Fund, Lindy Green Family Foundation and The Princess Margaret Foundation. The authors declare no other conflicts of interest.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2023.2191707

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.