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Saurabh Pancholi, Timothy Grosel, James B Massengill, Robert Pilarski, Frederick H Davidorf, Colleen M Cebulla, Mohamed H Abdel-Rehman; Somatic Alterations in Uveal Melanoma Tumors from Patients with Strong Personal and/or Family History of Cancer. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2831.
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© ARVO (1962-2015); The Authors (2016-present)
About 12% of uveal melanoma patients have strong personal or family history of cancer. The goal of this study was to assess the frequency of somatic variation in genes commonly reported in uveal melanoma (UM) tumors.
Patients with familial UM and/or history of at least two primary cancers in self, first or second degree relatives were included. Somatic mutations in BAP1, GNAQ, GNA11, PLCB4, SF3B1, CYSLTR2, and EIF1AX were assessed. Somatic mutations were assessed by direct (Sanger sequencing) in 27 tumors and by whole exome sequencing in nine. For GNAQ, GNA11, PLCB4, SF3B1, PLCB4 and CYSLTR2 the genome regions of mutational hot-spots were tested. For BAP1 the coding and adjacent non-coding regions were sequenced. Chromosome 3 copy number was also assessed. Germline mutations in known cancer genes were previously assessed in the majority of patients.
A total of 35 tumors from patients with strong personal and/or family history of cancer were studied, including 18 males and 17 females with an average age of 60 years (range 27-87). The cohort included four patients with familial UM, six with personal and/or family history of cutaneous melanoma or renal cell carcinoma (two tumors associated with BAP1-Tumor Predisposition Syndrome), and 25 patients with personal and/or family histories of other cancers. We identified 0/35 (0%) variants in EIF1AX, 4/33 (12.1%) in SF3B1, 17/34 (50.0%) in GNA11, 11/33 (33.3%) in GNAQ, 1/32 (3.1%) in PLCB4, 2/32 (6.3%) in CYSLTR2 and 23/35 (65.7%) in BAP1. One patient with no detectable BAP1 pathogenic alterations had monosomy of chromosome 3. In total BAP1 pathogenic variants and/or monosomy of chromosome 3 were identified in 24/35 (68.6%) patients.
Our results suggest that tumors from UM patients with strong personal and/or family history of cancers are more commonly aggressive molecular class 2 tumors.
This is a 2020 ARVO Annual Meeting abstract.
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