Current Bioinformatics Seminar
Time: 11AM Tuesdays.
Venue: Davis Auditorium and Online
29 July 2025
Recurrent intra-tumour heterogeneity is a hallmark of metastatic prostate cancer
Sirui WengPeter MacCallum Cancer Centre
Tumour heterogeneity originates from the interplay between the clonal evolution, the microenvironment and tumour plasticity during cancer evolution. Metastatic castration-resistant prostate cancer (mCRPC) is clinically highly heterogenous, posing great challenges on designing targeting therapeutics. However, to date, an integrated understanding of how these players lead to various level of heterogeneity in advanced prostate cancer remains unknown. To address this, 34 mCRPC lesions from 9 patients, with multiple lesions from individuals collected, were profiled with single-cell multi-omics and whole-genome sequencing. Despite limited driving force of microenvironment to tumour transcriptional heterogeneity, the clonal evolution primarily only brought genetic noise. Oppositely, we found recurrent tumour cell populations characterised the intra-tumour heterogeneity playing as functional unit of tumour ecosystem through archetype analysis. Surprisingly, there was a functional convergence between these recurrent intra-tumour populations, showing the systematic selection pressure on overall heterogeneity of metastatic prostate tumours. In summary, the finding described the transcriptional intra-tumour heterogeneity as a fundamental evolutionary unit independent from genetic and microenvironment factors, which also gives clinical implication on the heterogeneous expression of therapeutic targets like PSMA.