Spatial Transcriptomics Reveals Discrete Tumor Microenvironments and Autocrine Loops Within Ovarian Cancer Subclones

Ovarian masses from patients with high grade serous ovarian carcinoma undergoing debulking surgery were subjected to spatial transcriptomics profiling using the 10x Genomics Visium (fresh frozen) platform. Copy number inference using inferCNV predicted the presence of subclones with mutually exclusive copy number alterations (CNAs) in 5 of the 8 patient samples studied. In one patient, 3 subclones were predicted. For this patient sample, a serial section of the same tumor was used to microdissect regions corresponding to each of these subclones, and a 'normal' region predicted to contain only fibroblasts and no tumor cells. These microdissected regions were processed for low pass whole genome sequencing (WGS) and CNAs recorded using ichorCNA. An oral biopsy lacking tumor cells from an unrelated donor was used as a negative control for CNA inference. The CNAs predicted by inferCNV for the three subclones were validated by the low pass WGS and no CNAs were observed in the normal region containing fibroblasts.]]>
Inclusion: Cancer patients who provided informed consent to donate resections or biopsies that were being taken as part of their normal course of treatment or diagnosis.]]>
2020 - Visium spatial profiling of 8 HGSOC samples2020 - Computational analyses including inferCNV2021 - Low pass WGS on microdissected sample from Patient 1 -> confirmed subclones2022 - Paper submitted and preprint submitted online: doi.org 2023 - Paper revisions including, CosMx single molecular imaging technology applied to samples from patient 52024 - Paper accepted]]>