Abstract:
:The aim of the study was to investigate the molecular genetics of uveal melanoma (UM) metastases and correlate it with disease progression. Twelve pathologically confirmed UM metastases from 11 patients were included. Molecular genetic alterations in chromosomes 3 (including the BAP1 region), 8q, 6p, and 1p were investigated by microsatellite genotyping. Mutations in codon 209 of GNAQ and GNA11 genes were studied by restriction-fragment length polymorphism (RFLP). We identified monosomy of chromosome 3 in tumors from four patients with an average survival of 5 months (range 1-8 months) from time of diagnosis of metastatic disease. In contrast, tumors with either disomy or partial chromosome 3 alterations showed significantly slower metastatic disease progression with an average survival of 69 months (range 40-123 months, p = 0.003). Alterations in chromosomal arms 1p, 6p, and 8q and mutations in either GNAQ or GNA11 showed no association with disease progression. Prominent mononuclear inflammatory infiltrate was observed in tumors from patients with slowly progressive disease. In conclusion, in UM metastases, monosomy 3 is associated with highly aggressive, rapidly progressive disease while disomy or partial change of 3 and prominent mononuclear inflammatory infiltrate in the tumor is associated with better prognosis. These findings should be considered when designing clinical trials testing effectiveness of various therapies of metastatic UM.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Abdel-Rahman MH,Cebulla CM,Verma V,Christopher BN,Carson WE 3rd,Olencki T,Davidorf FHdoi
10.1016/j.exer.2012.04.010subject
Has Abstractpub_date
2012-07-01 00:00:00pages
26-31eissn
0014-4835issn
1096-0007pii
S0014-4835(12)00128-5journal_volume
100pub_type
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