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Antonio Pineiro, Paula Silva, Lourdes Loidi, Maria Santiago-Varela, Manuel F Bande, Maria Pardo, María José Blanco; Searching for genes predisposing to bilateral Uveal Melanoma (bUM) by exome sequencing of three unrelated cases. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3957.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) is the most common primary intraocular tumor in adults, with an annual incidence of approximately 6 cases per million people. Bilateral Uveal Melanoma (bUM) is rarer than UM with about 50 well-documented cases published since 1930. Considering its extremely low incidence, we hypothesize that it is very unlikely to find patients suffering from bUM in the same geographical region unless some shared genetic background predisposes to it.The aim of this study is to identify germline causing and/or predisposing genetic variants in 3 patients diagnosed of bUM.
We perform a retrospective study in 3 unrelated Caucasian patients (2 men and 1 woman) with ages of 80, 56 and 96 year-old, diagnosed and treated of bUM. Complete ophthalmic examination and ocular ultrasonographic study were carried out in both eyes of each patient. A complete screening of the systemic disease was performed in all of them. All patients signed a special informed consent to start a full genomic study, both in the pathological pieces from two eyes enucleated from two patients and blood samples. Exome sequencing was performed in DNA obtained from blood samples of the 3 bUM patients (IonTorrentTM PGM® System platform, Thermo Fisher). Data obtained from Exome sequencing were screened for shared germline rare genetic variants in the main genes related to UM (35 genes) by the 3 bUM cases.In addition, some common genetic background in non-coding flanking regions of these genes was investigated.
We found no rare variants shared by the 3 cases of bUM in the major genes related to UM. These results suggested an independent genetic way of developing bUM. Even tough, we found a shared genetic profile in some genes related to UM as GNAQ, CDKN2A, IGF1R, TP53, CDH5, VEGFA, HGF and CXCR4.Most of the shared variants have high population frequencies and are situated in non-coding flanking regions. However, it is not possible to rule out that this genetic profile is to some increase risk of developing bUM.
The cause of developing a bUM is apparently not linked to the existence of rare genetic variants in common UM genes. Further studies should be made to better confirm or refute the existence of a genetic profile that increase the risk of developing bUM. Next step of the study will be focused in searching for new predisposing genes for bUM.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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