June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Germline MBD4 variants in uveal melanoma patients
Author Affiliations & Notes
  • Mohamed H Abdel-Rahman
    Ophthalmology, The Ohio State University, Columbus, Ohio, United States
    Division of Human Genetics, The Ohio State University, Columbus, Ohio, United States
  • Peter Johansson
    Oncogenomics Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  • Frederick H Davidorf
    Ophthalmology, The Ohio State University, Columbus, Ohio, United States
  • Nicholas Hayward
    Oncogenomics Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  • Colleen M Cebulla
    Ophthalmology, The Ohio State University, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Mohamed Abdel-Rahman None; Peter Johansson None; Frederick Davidorf None; Nicholas Hayward None; Colleen Cebulla None
  • Footnotes
    Support  Patti Blow Research Fund in Ophthalmology; funds from the Ohio Lions Eye Research Foundation; grants from the National Cancer Institute at the National Institutes of Health (grants R21CA191943 [MHA], R21CA219884 [MHA], a cancer center core grant 2P30CA016058-40
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2354 – A0023. doi:
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    • Get Citation

      Mohamed H Abdel-Rahman, Peter Johansson, Frederick H Davidorf, Nicholas Hayward, Colleen M Cebulla; Germline MBD4 variants in uveal melanoma patients. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2354 – A0023.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : There is variable data regarding the frequency of germline MBD4 variants in patients with uveal melanoma (UM). The frequencies of pathogenic/likely pathogenic (P/LP) variants range from ~0.7% (8/1099) in a French cohort to 0.23% (1/432) in a Finnish cohort with no loss of function variants detected in the Finnish cohort. This casts doubt on the association of germline MBD4 variants and UM predisposition. Therefore, the goal of this study was to evaluate the frequency of MBD4 variants in a cohort of UM patients with strong personal and/or family history of cancer.

Methods : Germline variants in MBD4 were assessed in 182 UM patients with strong personal and/or family history of cancer including 27 patients with familial UM. Screening was carried out by next generation sequencing of individual or pooled samples (8 samples/pool) and all detected variants were confirmed by Sanger sequencing. Mutation burden was available in one patient that was included in The Cancer Genome Atlas (TCGA) project.

Results : Three patients (1.65%), all females, had germline P/LP variants in MBD4, which was significantly higher than in the European, Non-Finnish, general non-cancer population (Fisher’s exact 2-tailed p =0.001, RR 95% CI: 15.96 (5.1-50.4)). The ages of these patients were 41, 58, and 71 years. The 41-year-old female had multiple family members affected with breast and colon cancer. She was recurrence free at 91 months after enucleation of her large monosomy 3 (M3) tumor, with very high mutation burden. The 58-year-old female died shortly after diagnosis and treatment of her UM from an unrelated cause. She reported a family history of throat cancer in her father and unknown cancers in her maternal and paternal cousins. The 71 year-old-female, had a history of two additional relatives on the same side of the family with UM. Germline DNA was available on one of them and he tested negative for the MBD4 pathogenic variant.

Conclusions : Our results support a role for MBD4 P/LP variants in predisposition to UM, likely through modifying the effect of other cancer predisposition genes. Further studies of the clinical phenotype of subjects with germline pathogenic variants are warranted.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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