Elevated NSD3 histone methylation activity drives squamous cell lung cancer.

ABSTRACT: Amplification of chromosomal region 8p11-12 is a common genetic alteration that has been implicated in the aetiology of lung squamous cell carcinoma (LUSC)^1-3. The FGFR1 gene is the main candidate driver of tumorigenesis within this region⁴. However, clinical trials evaluating FGFR1 inhibition as a targeted therapy have been unsuccessful⁵. Here we identify the histone H3 lysine 36 (H3K36) methyltransferase NSD3, the gene for which is located in the 8p11-12 amplicon, as a key regulator of LUSC tumorigenesis. In contrast to other 8p11-12 candidate LUSC drivers, increased expression of NSD3 correlated strongly with its gene amplification. Ablation of NSD3, but not of FGFR1, attenuated tumour growth and extended survival in a mouse model of LUSC. We identify an

SUBMITTER: Yuan G 

PROVIDER: S-EPMC7895461 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature