The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group

Natasha M. van Poppelen*, Nathalie Cassoux, Joni A. Turunen, Nicole C. Naus, Robert M. Verdijk, Jolanda Vaarwater, Victoria Cohen, Vasilios P. Papastefanou, Hayyam Kiratli, Svetlana V. Saakyan, Alexander Y. Tsygankov, Iwona Rospond-Kubiak, Hardeep S. Mudhar, Sachin M. Salvi, Jens F. Kiilgaard, Steffen Heegaard, Alexandre P. Moulin, Maria A. Saornil, Ciro Garciá-Alvarez, Maria FiliNils A. Eide, Peter Meyer, Tero T. Kivela, Annelies de Klein, Emine Kilic, Ranaa T. Al-Jamal

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

PURPOSE:

To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. 

METHODS:

Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. 

RESULTS:

The mean age at diagnosis was 17 years (range 5.0–24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). 

CONCLUSIONS:

We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

Original languageEnglish
JournalInvestigative Ophthalmology and Visual Science
Volume65
Issue number4
DOIs
Publication statusPublished - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 Association for Research in Vision and Ophthalmology Inc.. All rights reserved.

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