All Eyes on Epigenetics

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Science  10 Feb 2012:
Vol. 335, Issue 6069, pp. 637
DOI: 10.1126/science.335.6069.637-b

Cancer geneticists who are cataloging the genes mutated in human tumors have encountered a recurring theme: Many tumor types carry mutations in genes implicated in epigenetic mechanisms that regulate gene expression. New work on a rare childhood eye cancer called retinoblastoma reinforces the notion that the development and behavior of tumors involve both genetic and epigenetic mechanisms. Retinoblastoma arises when both copies of a tumor suppressor gene called RB1 are inactivated. It had been postulated that RB1 loss destabilizes the genome, leading to the accumulation of additional mutations that increase tumor aggressiveness. Through whole-genome sequencing of four retinoblastoma samples, Zhang et al. instead discovered that these tumors have a low mutation rate and a stable genome. However, several known oncogenes and tumor suppressor genes were found to have epigenetic changes that correlated with changes in their expression pattern in tumor versus normal tissue. Thus, RB1 mutational status appears to affect the epigenetic mechanisms that turn genes on and off. One of the genes overexpressed in retinoblastoma encodes the protein tyrosine kinase SYK, and experiments with preclinical models suggest that SYK inhibitors may be useful drugs for targeting this type of tumor.

Nature 10.1038/nature10733 (2012).

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