Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry.

ABSTRACT: Childhood high-risk neuroblastomas with MYCN gene amplification are difficult to treat effectively¹. This has focused attention on tumor-specific gene dependencies that underlie tumorigenesis and thus provide valuable targets for the development of novel therapeutics. Using unbiased genome-scale CRISPR-Cas9 approaches to detect genes involved in tumor cell growth and survival^2-6, we identified 147 candidate gene dependencies selective for MYCN-amplified neuroblastoma cell lines, compared to over 300 other human cancer cell lines. We then used genome-wide chromatin-immunoprecipitation coupled to high-throughput sequencing analysis to demonstrate that a small number of essential transcription factors-MYCN, HAND2, ISL1, PHOX2B, GATA3, and TBX2-are members of the transcri

SUBMITTER: Durbin AD 

PROVIDER: S-EPMC6386470 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature