Molecular profiling of primary uveal melanoma: results of a Polish cohort

Abstract

There is no published data regarding the molecular alterations of Polish patients with primary uveal melanoma. We performed whole exome sequencing of 20 primary uveal melanomas (UMs), 10 metastasizing and 10 non-metastasizing cases to identify significant molecular alterations. We detected mutations and copy number variants in the BAP1 gene in 50% (10 cases) of the cases. GNA11 mutations were detected in 50% (10 cases) including nine p.Q209L and one p.R183C. GNAQ mutations gene were detected in 40% (8 cases) and all were p.Q209P. SF3B1, EIF1AX, PLCB4, and PALB2 mutations were detected in one case each. Genetic aberrations of FBXW7 were detected in 55% of cases, with copy number loss of 10 and missense mutation in one. Gain or loss of copy number was observed in 60%, 60%, and 10% of cases in MYC, MLH1, and CDKN2A genes, respectively. BAP1 and GNAQ tumor suppressor genes are more often mutated in UM with metastasis, while GNA11 mutations are more frequently detected in non-metastasizing tumors. MYC copy gain was present twice as frequently (80% versus 40%) in cases with versus those without metastases. BAP1 mutation correlated with worse overall survival; while GNA11 mutation and CDKN2A loss correlated with better and worse progression-free survival, respectively. We have confirmed BAP1 prognostic potential and documented frequent MYC amplification in metastasizing cases. Although GNA11 mutation and CDKN2A loss significantly correlated with progression-free survival in our study, our sample size is small. The prognostic significance of GNAQ/GNA11 mutation and CDKN2A loss would require further investigation. Melanoma Res 33: 104-115

Whole Exome Sequencing of Thymoma Patients Exhibiting Exceptional Responses to Pemetrexed Monotherapy

“…A homozygous missense mutation in STIL causes holoprosencephaly and microcephaly [ 59 ]. In one study, genetic aberrations in FBXW7 were detected in 55% of patients with primary uveal melanoma [ 60 ]. A recent study showed that EPHA5 mutations, along with other molecular alterations in the DNA damage response pathway and a favorable antitumor immune signature, could contribute to exceptional responses [ 61 ].…”

Das Aderhautmelanom im Zeitalter der generativen künstlichen Intelligenz – im Gespräch mit ChatGPT

“…Hier werden von ChatGPT richtigerweise Mutationen in den GNA11- und GNAQ-Genen sowie im BAP-1-Gen erwähnt. Allerdings wird das CDKN2A-Gen auch aufgelistet, das beim AHM nur selten eine Rolle spielt 7 , aber eher bei einer Vielzahl von anderen Tumoren 8 , 9 , 10 . Interessanterweise ist die Alternativantwort hier wesentlich passender, dadurch, dass das CDKN2A-Gen nicht erwähnt wird, dafür aber das EIF1AX-Gen. Schließlich bleibt noch anzumerken, dass tumoreigene Mutationen und somatische Mutationen in beiden Antworten gleichgestellt werden, indem Menschen mit solchen Genmutationen empfohlen wird, sich regelmäßig augenärztlich untersuchen zu lassen.…”