Oral Presentation 45th Lorne Genome Conference 2024

Studying ovarian cancer subclones and their microenvironments using spatial transcriptomics   (#36)

Elena Denisenko 1 , Leanne de Kock 1 , Adeline Tan 1 , Aaron Beasley 1 , Maria Beilin 1 , Matthew Jones 1 , Rui Hou 1 , Dáithí Ó Muirí 1 , Sanela Bilic 1 , G. Raj K. A. Mohan 1 , Stuart Salfinger 1 , Simon Fox 1 , Khaing Hmon 1 , Yen Yeow 1 , Youngmi Kim 1 , Rhea John 1 , Tami Gilderman 1 , Emily Killingbeck 1 , Elin Gray 1 , Paul Cohen 1 , Yu Yu 1 , Alistair Forrest 1
  1. Harry Perkins Institute for Medical Research, Nedlands, WA, Australia

High-grade serous ovarian carcinoma (HGSOC) is a polyclonal disease characterised by the presence of subclones with distinct cancer genotypes. This intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and overall poor prognosis. Here, we used spatial transcriptomics platforms (10x Genomics Visium and NanoString CosMx Spatial Molecular Imaging (SMI)) to examine genetic heterogeneity of HGSOC cells and their association with infiltrating populations in samples from patients treated with neoadjuvant chemotherapy. We found evidence of multiple tumour subclones with different copy number alterations co-existing within individual tumour sections. Examining gene expression differences between subclones we found evidence that their cell-to-cell communication networks may be rewired by differences in ligand and receptor expression levels. We hypothesise that this may modulate their interactions with stromal and immune cells and likely also leads to the creation of subclone specific autocrine loops.