| First Author | Avgustinova A | Year | 2018 |
| Journal | Nat Cell Biol | Volume | 20 |
| Issue | 12 | Pages | 1400-1409 |
| PubMed ID | 30455462 | Mgi Jnum | J:269797 |
| Mgi Id | MGI:6271559 | Doi | 10.1038/s41556-018-0233-x |
| Citation | Avgustinova A, et al. (2018) Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours. Nat Cell Biol 20(12):1400-1409 |
| abstractText | Mutations in, and the altered expression of, epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive antitumour targets. The open-versus-closed chromatin state within the cells-of-origin of cancer correlates with the uneven distribution of mutations. However, the long-term effect of targeting epigenetic modifiers on mutability in patients with cancer is unclear. Here, we increased chromatin accessibility by deleting the histone H3 lysine 9 (H3K9) methyltransferase G9a in murine epidermis and show that this does not alter the single nucleotide variant burden or global genomic distribution in chemical mutagen-induced squamous tumours. G9a-depleted tumours develop after a prolonged latency compared with their wild-type counterparts, but are more aggressive and have an expanded cancer progenitor pool, pronounced genomic instability and frequent loss-of-function p53 mutations. Thus, we call for caution when assessing long-term therapeutic benefits of chromatin modifier inhibitors, which may promote more aggressive disease. |
