High-resolution structural genomics reveals new therapeutic vulnerabilities in glioblastoma

We investigated the role of 3D genome architecture in instructing functional properties of glioblastoma stem cells (GSCs) by generating the highest-resolution 3D genome maps to-date for this cancer. Integration of DNA contact maps with chromatin and transcriptional profiles identified specific mechanisms of gene regulation, including individual physical interactions between regulatory regions and their target genes. Residing in structurally conserved regions in GSCs was CD276, a gene known to play a role in immuno-modulation. We show that, unexpectedly, CD276 is part of a stemness network in GSCs and can be targeted with an antibody-drug conjugate to curb self-renewal, a key stemness property. Our results demonstrate that integrated structural genomics datasets can be employed to rationally identify therapeutic vulnerabilities in self-renewing cells.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001004968	High-resolution (Sub-5 kbp resolution) Hi-C datasets generated using glioblastoma primary cultures from 3 different adult patients.	Illumina HiSeq 2500 NextSeq 500	6

Publications	Citations
High-resolution structural genomics reveals new therapeutic vulnerabilities in glioblastoma. Johnston MJ, Nikolic A, Ninkovic N, Guilhamon P, Cavalli FMG, Seaman S, Zemp FJ, Lee J, Abdelkareem A, Ellestad K, Murison A, Kushida MM, Coutinho FJ, Ma Y, Mungall AJ, Moore R, Marra MA, Taylor MD, Dirks PB, Pugh TJ, Morrissy S, St Croix B, Mahoney DJ, Lupien M, Gallo M. Genome Res 29: 2019 1211-1222	42