<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>We have investigated the frequency of methylation of several tumour suppressor genes in uveal melanoma. As the loss of one copy of chromosome 3 (monosomy 3),
which is found in about half of these tumours, is tightly associated with metastatic
disease, a special emphasis was laid on genes located on this chromosome, including
the fragile histidine triad (<italic>FHIT</italic>), von Hippel–Lindau (<italic>VHL</italic>), β-catenin (<italic>CTNNB1</italic>),
activated leukocyte cell adhesion molecule (<italic>ALCAM</italic>) and retinoic acid receptor-β2
(<italic>RARB</italic>) genes. In addition, the methylation patterns of the CpG-rich regions 5′
of the E-cadherin (<italic>CDH1</italic>), p16/cyclin-dependent kinase inhibitor 2 A (<italic>CDKN2A</italic>)
and retinoblastoma (<italic>RB1</italic>) genes were analysed by bisulphite genomic sequencing or
methylation-specific PCR (MSP). Furthermore, the SNRPN and <italic>D15S63</italic> loci, which
are located in the imprinted region of chromosome 15, were included in the study.
Aberrant methylation was detected in nine of 40 tumours analysed: The imprinted
<italic>SNRPN</italic> and <italic>D15S63</italic> loci were hypermethylated in three tumours, all of which retained
both copies of chromosome 3. Methylated <italic>RARB</italic> alleles were detected in three
tumours, whereas in three other tumours <italic>CDKN2A</italic> was found to be methylated.
As we did not find RARB and CDKN2A preferentially methylated in tumours with
monosomy 3, which is a significant predictor of metastatic disease, we suggest that
these genes may play a causative role in the formation of uveal melanoma but not in
the development of metastases.</p>
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Comp Funct Genomics. 2003 Jun; 4(3):329-336