POSTERS
AACR 2026 | poster #7235
Integrated spatial multiomic profiling of 3D genome architecture and transcriptome-wide gene expression in breast cancer models
highlights
Multi-platform analysis of 3D genome organization and spatial transcriptomics enabled investigation into the role of genome structure in transcriptomic gene expression in ER+ MCF7 breast cancer cells compared to MCF10a breast cells.
The combined approach of PaintScape and CosMx revealed how disruptions in genome organization drive disease mechanisms in ER⁺ breast cancer by linking altered chromatin topology to dysregulated expression of key oncogenic pathway genes.
PaintScape revealed distinct copy number variations (amplifications and deletions) directly in situ in single cells and in cell sub-populations such as:
specific gains in Chr17q and 20q regions containing DEREs in MCF7 cells
focal amplification of key oncogenes BRIP1, MYC, SNAI1
loss of CDKN2A gene on Chr 9
PaintScape also revealed ploidy variation of whole chromosome and sub-chromosomal regions as well as inter-chromosomal interactions, potential translocations, and the simultaneous proximity of multi-loci interactions in situ in single cells:
for example, the close proximity of chromosomes 3, 5 and 9 regions in MCF10a consistent with known translocations t(3;5;9) and t(3;9)
the close proximity of GATA3 (Chr10) and HOXA (Chr7) loci in MCF7 causing dysregulated gene expression of GATA3 and certain HOXA genes in MCF7
PaintScape revealed ecDNA copy number, structure, nuclear locations and in situ interactions:
a significant fraction of the BRIP1 ecDNA formed self-interacting hub like structures in single MCF7 cells
BRIP1 ecDNA closely interacts with amplified DEREs on Chr20q including SNAI1 oncogene
CosMx WTX identified elevated expression of ER‑driven oncogenes GATA3 and CCND1 in MCF7 cells, consistent with enhanced estrogen‑dependent luminal signaling and proliferative activity
PaintScape 3D genome data shows increased enhancer-promoter interactions and strengthen intra-TAD interactions for these genes revealing mechanism of higher expression
PaintScape system characterized and directly visualized unique ecDNA structure containing relevant oncogenes BRIP1, TBX2, MED13 in MCF7
CosMx WTX shows higher expression of these genes in MCF7 compared to MCF10a revealing functional relevance of ecDNA amplification which promotes opportunistic enhancer hijacking within ecDNA elements and promoting dysregulated expression