Molecular and genetic features of iris and choroidal melanoma

Abstract

Purpose: Analysis of the frequency of molecular genetic aberrations in tumour tissue and blood in patients with iris melanoma.

Methods. 140 patients with uveal melanoma (UM) were analysed by methyl-sensitive PCR. The experimental group included 48 patients with iris melanoma (group A) and 62 patients with spread to the ciliary body (group B). Group C (comparison) consisted of 30 patients with melanoma in 2012.

Results. The spindle cell tumour type was significantly more frequent in subgroup 1p+8p (A) compared to subgroup M3+1p (A) (p=0.049), and the mixed cell type was more frequent in subgroup M3+1p (A) compared to subgroup 1p+8p (A) (p=0.049). In the subgroup of complete M3 (C), tumour spread to the ciliary body was significantly more often determined compared to other subgroups (p=0.035). In the partial M3 (C) subgroup, there was a significant association of the frequency of partial monosomy of chromosome 3 with mixed-cell and epithelioid-cell type UM (p=0.014 and 0.042, respectively). In iris melanoma, deletion of the entire short arm of chromosome 1 was found in 68.7%, chromosome 8 in 47.9%, with spread to the ciliary body in 77.4% and 51.6%, respectively, and in chorioideal melanoma in 30% and 20% of cases. No mutations in the GNAQ/GNA11 genes were detected in group A. In group B, one heterozygous mutation in GNAQ/GNA11 genes was detected in 2 patients. In group C, mutations in GNAQ/GNA11 genes were detected in 27 patients (90%). When comparing the frequency of heterozygous mutation in GNAQ/ GNA11 genes, significant differences were obtained between the experienced groups and the comparison group (F=0.0000001, χ² =56.45). The CC genotype of the C3435T polymorphic marker of the ABCB1 gene was found in 90% (F= 0.026418, χ² =5.36, significantly more frequent compared with group III) in group I, in 92.3% (F= 0.006183, χ² =7.75 significantly more frequent compared with group III) in group II, and in 60% in group III. TT genotype was not detected in any group.

Conclusion. The identified features confirm the more favourable nature of the tumour process in iris melanomas compared to choroidal melanomas.