In a recent research highlight in Genome Medicine (1), Matthias Schlesner and Roland Eils discuss the impact of genome hypermutation on the development of certain cancers. A recent study by Shlien et al. (2) describes that tumors from children with congenital biallelic mismatch repair deficiency (bMMRD) show an extremely high mutation rate (named "ultra-hypermutation”), exceeding even highly mutated adult cancers by one order of magnitude. Together with other studies on genome hypermutation in cancer, e.g. the earlier work of the eilslabs on X-Chromosome hypermutation (3), these findings might lead to the development of new therapeutic approaches to combat cancer.
Citations:
- (1) Schlesner, M., & Eils, R. (2015). Hypermutation takes the driver's seat. Genome Med, 7(1), 31. doi: 10.1186/s13073-015-0159-x
- (2) Shlien, A., Campbell, B. B., de Borja, R., Alexandrov, L. B., Merico, D., Wedge, D., . . . Biallelic Mismatch Repair Deficiency, C. (2015). Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Nat Genet, 47(3), 257-262. doi: 10.1038/ng.3202
- (3) Jäger, N., Schlesner, M., Jones, David T. W., Raffel, S., Mallm, J.-P., Junge, Kristin M., . . . Eils, R. (2013). Hypermutation of the Inactive X Chromosome Is a Frequent Event in Cancer. CELL, 155(3), 567-581. doi: 10.1016/j.cell.2013.09.042
