Saltar al contenido
Merck
  • Rewiring of the 3D genome during acquisition of carboplatin resistance in a triple-negative breast cancer patient-derived xenograft.

Rewiring of the 3D genome during acquisition of carboplatin resistance in a triple-negative breast cancer patient-derived xenograft.

Scientific reports (2023-04-04)
Mikhail G Dozmorov, Maggie A Marshall, Narmeen S Rashid, Jacqueline M Grible, Aaron Valentine, Amy L Olex, Kavita Murthy, Abhijit Chakraborty, Joaquin Reyna, Daniela Salgado Figueroa, Laura Hinojosa-Gonzalez, Erika Da-Inn Lee, Brittany A Baur, Sushmita Roy, Ferhat Ay, J Chuck Harrell
RESUMEN

Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (< 2 Mb) interactions, chromatin looping, formation of TAD, chromatin state switching into a more active state, and amplification of ATP-binding cassette transporters. Transcriptome changes suggested the role of long-noncoding RNAs in carboplatin resistance. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of aggressiveness-, metastasis- and other cancer-related pathways. Integrative analysis highlighted increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial energy metabolism. Our results suggest that 3D genome remodeling may be a key mechanism underlying carboplatin resistance.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Anti-MCUB antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-BRCA1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody