Miniatura

Fitxers

12541_5610944_nature_cell_saznar_fsupek.pdf (15.78 MB)

Tipus de document

Article

Versió

Versió acceptada

Data de publicació

2018-01-01

Tots els drets reservats

Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/176381

Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1038/s41556-018-0233-x

Resum

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.

Matèries

Epigenètica, Metàstasi, Càncer de pell

Matèries (anglès)

Epigenetics, Metastasis, Skin cancer

Citació

Col·leccions

Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

AVGUSTINOVA, Alexandra, SYMEONIDI, Aikaterini, CASTELLANOS, Andrés, URDIROZ URRICELQUI, Uxue, SOLÉ BOLDO, Llorenç, MARTÍN, Mercè, PÉREZ RODRÍGUEZ, Ivan, PRATS, Neus, LEHNER, Ben, SUPEK, Fran, AZNAR BENITAH, Salvador. Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours. _Nature Cell Biology_. 2018. Vol. 20, núm. 12, pàgs. 1400-1409. [consulta: 21 de gener de 2026]. ISSN: 1465-7392. [Disponible a: https://hdl.handle.net/2445/176381]

Exportar metadades

JSON - METS

Compartir registre