It has been proposed that in cancer, where the bulk of the genome becomes 
hypomethylated, there is an increase in transcriptional noise that might lead to 
the generation of antisense transcripts that could affect the function of key 
oncosuppressor genes, ultimately leading to malignant transformation. Here, we 
describe the computational identification of a melanoma-enriched antisense 
transcript, TRPM2-AS, mapped within the locus of TRPM2, an ion channel capable 
of mediating susceptibility to cell death. Analysis of the TRPM2-AS genomic 
region indicated the presence in the same region of another tumor-enriched TRPM2 
transcript, TRPM2-TE, located across a CpG island shared with TRPM2-AS. 
Quantitative PCR experiments confirmed that TRPM2-AS and TRPM2-TE transcripts 
were up-regulated in melanoma, and their activation was consistent with the 
methylation status of the shared CpG island. Functional knock-out of TRPM2-TE, 
as well as over-expression of wild-type TRPM2, increased melanoma susceptibility 
to apoptosis and necrosis. Finally, expression analysis in other cancer types 
indicated that TRPM2-AS and TRPM2-TE over-expression might have an even wider 
role than anticipated, reinforcing the relevance of our computational approach 
in identifying new potential therapeutic targets.