Heterogeneity of gross chromosomal abnormalities in uveal melanoma with extraocular extension detected by multiplex ligation-dependent probe amplification


Session type:

Sarah L. Lake1, Bertil E. Damato2, Justyna Dopierala1, Azzam F.G. Taktak3, Sarah E. Coupland1
1Pathology Department, School of Cancer Studies, University of Liverpool, Liverpool, United Kingdom,2Ocular Oncology Service, St Paul’s Eye Clinic, Royal Liverpool University Hospital, Liverpool, United Kingdom,3Department of Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Liverpool, United Kingdom


Uveal melanoma (UM) is the most common intra-ocular tumour in adults. Metastasis occurs hematogeneously to the liver in about 50% of patients and is almost always fatal.

In addition to clinical and histopathological features, UM is an unusual tumour in that gross chromosomal abnormalities are also strongly associated with poor prognosis. Prognostic testing for the most informative of these genetic changes is an invaluable part of routine care, allowing patients at high risk of metastasis to be more closely monitored and enrolled in the appropriate clinical trials.

The purpose of this study was to determine if tumours with the poor prognostic feature, extraocular extension, were heterogeneous for the most common gross chromosomal abnormalities associated with prognosis in UM on chromosomes 1p 3, 6 and 8.


Multiplex ligation-dependent probe amplification (MLPA) using the P027 assay was performed on formalin-fixed, paraffin-embedded sections from ten UM. The intraocular and extraocular areas of the tumour were microdissected and analyzed individually.


Of the ten UM analyzed, four were heterogeneous for copy number of at least one chromosome arm. No heterogeneity of 1p or 8p was observed. The most frequently heterogeneous chromosome arm was 6p. In one tumour MLPA revealed cells to be monosomy 3 in the intraocular area of the tumour but disomy 3 in the extraocular area of the tumour.


Heterogeneity of chromosome arm copy number, between the intraocular and extraocular areas, of UM with extraocular extension can be observed for chromosomes 3, 6 and 8q by MLPA. As monosomy 3 and polysomy 8q are the chromosomal abnormalities most strongly associated with poor prognosis in UM, these results suggest that both intraocular and extraocular areas of the tumour should be sampled to perform accurate genetic prognostic testing.