We performed comprehensive molecular analysis of five cases of metastasizing uveal malignant melanoma (UM) (fresh-frozen samples) with an NGS panel of 73 genes. A likely pathogenic germline TP53 mutation c.760A > G (p.I254V) was found in two tumor samples and matched nontumor tissue. In three cases, pathogenic BAP1 mutation was detected together with germline missense variants of uncertain significance in ATM. All cases carried recurrent activating GNAQ or GNA11 mutation. Moreover, we analyzed samples from another 16 patients with primary UM by direct Sanger sequencing focusing only on TP53 coding region. No other germline TP53 mutation was detected in these samples. Germline TP53 mutation, usually associated with Li-Fraumeni syndrome, is a rare event in UM. To the best of our knowledge, only one family with germline TP53 mutation has previously been described. In our study, we detected TP53 mutation in two patients without known family relationship. The identification of germline aberrations in TP53 or BAP1 is important to identify patients with Li-Fraumeni syndrome or BAP1 cancer syndrome, which is also crucial for proper genetic counseling.

• MeSH
• Ataxia Telangiectasia Mutated Proteins genetics   MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Middle Aged MeSH
• Humans MeSH
• Melanoma genetics   pathology   MeSH
• Survival Rate MeSH
• Young Adult MeSH
• DNA Mutational Analysis MeSH
• Tumor Suppressor Proteins genetics   MeSH
• Tumor Suppressor Protein p53 genetics   MeSH
• Liver Neoplasms genetics   secondary   MeSH
• Uveal Neoplasms genetics   pathology   MeSH
• Prognosis MeSH
• Aged MeSH
• Ubiquitin Thiolesterase genetics   MeSH
• Uveal Melanoma MeSH
• Germ-Line Mutation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• ATM protein, human MeSH Browser
• Ataxia Telangiectasia Mutated Proteins MeSH
• BAP1 protein, human MeSH Browser
• Tumor Suppressor Proteins MeSH
• Tumor Suppressor Protein p53 MeSH
• Ubiquitin Thiolesterase MeSH
• TP53 protein, human MeSH Browser