Abstract
Purpose :
Mutations in Uveal Melanoma, such as those in the genes EIF1AX, SF3B1 and BAP1, affect prognosis, but also tumour inflammation. Especially mutations in BAP1/Monosomy 3 (M3) are associated with an inflammatory phenotype, but cases without BAP1/M3 aberration may also demonstrate an increased leukocyte influx and increased HLA expression. This study tested the hypothesis that mutations in GNA11 or GNAQ may play a role in the inflammatory response and influence progression of the disease, independent of the chromosome 3 status.
Methods :
We analysed the data of 59 patients from the LUMC, The Netherlands. Clinical and pathological parameters were determined after enucleation. The type of GNAQ/11 mutation was analysed using ddPCR, chromosome aberrations by SNP analysis, and HLA expression by Illumina PCR. M3 tumours were analysed separately from Disomy 3 (D3) tumours. We analysed the following group sizes: D3+GNA11: n=9, D3+GNAQ n=12, M3+GNA11 n=23, M3+GNAQ n=15. D3+Q209L n=15, D3+Q209P n=6, M3+Q209L n=27 and M3+Q209P n=11.
Results :
Comparing the GNAQ-mutated D3 tumours with mutated GNA11-D3 tumours yielded no significant differences in histopathological characteristics. This was the case for the comparison between the GNAQ/GNA11-M3 tumours as well. When comparing the Q209L mutations with Q209P mutations in M3 tumours, a higher mitotic count was found in Q209P/M3 tumours (p=0.007). No significant differences were found between the Q209P/Q209L-D3 groups. KM-curves between the patients of the different groups were not significantly different. Expression of HLA Class I antigens did not differ between tumours with GNAQ or GNA11 mutations, or between Q209P/Q209L mutations. The only significant difference in HLA Class I expression came from the difference between M3 and D3 tumours.
Conclusions :
The type of mutation (Q209P/Q209L) and location of mutation (GNA11/GNAQ) did not have a significant effect on HLA Class I expression or survival, which was opposite to our hypothesis. These early mutations therefore do not explain the difference in inflammation or development of the disease between tumours that share the same chromosome 3 status.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.