Simone L Scholz1, Inga Möller2, Henning Reis3, Daniela Süßkind4, Johannes A P van de Nes5, Sonia Leonardelli2, Bastian Schilling6, Elisabeth Livingstone2, Tobias Schimming2, Annette Paschen2, Antje Sucker2, Rajmohan Murali7, Klaus-Peter Steuhl1, Dirk Schadendorf2, Henrike Westekemper1, Klaus G Griewank8. 1. Department of Ophthalmology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany. 2. Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany. 3. Institute of Pathology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany. 4. Department of Ophthalmology, University Hospital Tübingen, Tübingen, Germany. 5. Institute of Pathology, Ruhr University Bochum, Bochum, Germany. 6. Department of Dermatology, University Hospital Würzburg, Würzburg, Germany. 7. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States. 8. Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), Essen, Germany 8Dermatopathologie bei Mainz, Nieder-Olm, Germany.
Abstract
Purpose: The most common malignant intraocular tumors with a high mortality in adults are uveal melanomas. Uveal melanomas arise most frequently in the choroid or ciliary body (97%) and rarely in the iris (3%). Whereas conjunctival and posterior uveal (ciliary body and choroidal) melanomas have been studied in more detail genetically, little data exist regarding iris melanomas. Methods: In our study, we genetically analyzed 19 iris melanomas, 8 ciliary body melanomas, 3 ring melanomas, and 4 iris nevi. A targeted next-generation sequencing approach was applied, covering the mutational hotspot regions of nine genes known to be mutated in conjunctival and uveal melanoma (BRAF, NRAS, KIT, GNAQ, GNA11, CYSLTR2, SF3B1, EIF1AX, and BAP1). Results: Activating GNAQ or GNA11 hotspot mutations were detected in a mutually exclusive fashion in 84% (16/19) of iris melanomas. EIF1AX gene mutations also were frequent, detected in 42% (8/19) of iris melanomas. In 4 iris nevi, one GNAQ mutation was identified. GNAQ, GNA11, EIF1AX, and BAP1 mutations were identified at varying frequencies in ciliary body and ring melanomas. Conclusions: In this most comprehensive genetic analysis of iris melanomas published to date, we find iris melanomas to be related genetically to choroidal and ciliary body melanomas, frequently harboring GNAQ, GNA11, and EIF1AX mutations. Future studies will need to assess if screening mutation profiles in iris melanomas may be of diagnostic or prognostic value.
Purpose: The most common malignant intraocular tumors with a high mortality in adults are uveal melanomas. Uveal melanomas arise most frequently in the choroid or ciliary body (97%) and rarely in the iris (3%). Whereas conjunctival and posterior uveal (ciliary body and choroidal) melanomas have been studied in more detail genetically, little data exist regarding iris melanomas. Methods: In our study, we genetically analyzed 19 iris melanomas, 8 ciliary body melanomas, 3 ring melanomas, and 4 iris nevi. A targeted next-generation sequencing approach was applied, covering the mutational hotspot regions of nine genes known to be mutated in conjunctival and uveal melanoma (BRAF, NRAS, KIT, GNAQ, GNA11, CYSLTR2, SF3B1, EIF1AX, and BAP1). Results: Activating GNAQ or GNA11 hotspot mutations were detected in a mutually exclusive fashion in 84% (16/19) of iris melanomas. EIF1AX gene mutations also were frequent, detected in 42% (8/19) of iris melanomas. In 4 iris nevi, one GNAQ mutation was identified. GNAQ, GNA11, EIF1AX, and BAP1 mutations were identified at varying frequencies in ciliary body and ring melanomas. Conclusions: In this most comprehensive genetic analysis of iris melanomas published to date, we find iris melanomas to be related genetically to choroidal and ciliary body melanomas, frequently harboring GNAQ, GNA11, and EIF1AX mutations. Future studies will need to assess if screening mutation profiles in iris melanomas may be of diagnostic or prognostic value.
Authors: Susan Kennedy; Michael Rice; Sinead Toomey; Noel Horgan; Bryan T Hennessey; Annemarie Larkin Journal: J Cancer Res Clin Oncol Date: 2018-07-14 Impact factor: 4.553
Authors: Natasha M van Poppelen; Daniël P de Bruyn; Tolga Bicer; Rob Verdijk; Nicole Naus; Hanneke Mensink; Dion Paridaens; Annelies de Klein; Erwin Brosens; Emine Kiliҫ Journal: Int J Mol Sci Date: 2020-12-30 Impact factor: 5.923
Authors: Laurien E Houtzagers; Annemijn P A Wierenga; Aleid A M Ruys; Gregorius P M Luyten; Martine J Jager Journal: Int J Mol Sci Date: 2020-09-28 Impact factor: 5.923
Authors: Adam Ustaszewski; Joanna Janowska-Głowacka; Katarzyna Wołyńska; Anna Pietrzak; Magdalena Badura-Stronka Journal: Arch Med Sci Date: 2020-02-25 Impact factor: 3.318