Monosomy 3 status of uveal melanoma metastases is associated with rapidly progressive tumors and short survival.

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 Res

authors

Abdel-Rahman MH,Cebulla CM,Verma V,Christopher BN,Carson WE 3rd,Olencki T,Davidorf FH

doi

10.1016/j.exer.2012.04.010

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

26-31

eissn

0014-4835

issn

1096-0007

pii

S0014-4835(12)00128-5

journal_volume

100

pub_type

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