tumoral genomic losses affecting noncoding genes

Cancer-associated chromosomal losses may act through inactivation of genes that do not encode proteins. For example, several genomic regions that are recurrently deleted in a variety of tumors contain microRNA genes (miRNAs).

These genes encode small RNAs (sRNAs) involved in post-transcriptional regulation of gene expression, and there is growing evidence that the loss of specific microRNAs with tumor-suppressive activity may contribute to tumorigenesis.

This pathogenetic mechanism was shown by the observation that MIRN15A and MIRN16-1 are located within a segment of band 13q14.3 that is deleted in approximately 50% of patients with chronic lymphocytic leukemia and the subsequent discovery that MIRN15A and MIRN16-1 negatively regulate the expression of the antiapoptotic protein BCL2.

Given that many chromosomal regions that are recurrently deleted in cancer appear to lack protein-coding genes that normally act to limit cell proliferation, it seems plausible that the analysis of cancer-associated genomic losses will reveal additional tumor-suppressor microRNAs.

References

 Fröhling S, Döhner H. Chromosomal abnormalities in cancer. N Engl J Med. 2008 Aug 14;359(7):722-34. PMID: #18703475#