From cfDNA to RNA abundance

Background

1) Tumor cells shed highly-fragmented DNA into the bloodstream which can be retrieved via a routine blood draw (termed “liquid biopsy”). This technology enables us to deeply characterize individual patients’ tumour DNA without the need for an invasive tissue biopsy.

2) Recent studies suggest that DNA fragmentation patterns in blood can be used to determine gene expression activities via recovering nucleosome positioning at regions critical for gene expression such as transcription start sites.

Objectives

Our objective was to determine if 1) tumour DNA fragments in blood could infer tumour gene expression activity and 2) reveal insights into other tumour characteristics.

Results

We performed deep genomic sequencing on the DNA from 62 patient blood samples with metastatic prostate cancer. We found that tumour DNA fragments in blood could be leveraged to gain information about tumour gene activity, identify different prostate cancer subtypes, and monitor tumour evolution in response to cancer treatment.

Publication

Herberts, C.^†, Annala, M.^†, Sipola, J.^†, Ng, S. W., Chen, X. E., Nurminen, A., ... & Wyatt, A. W. (2022). Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer. Nature, 608(7921), 199-208. doi.org/10.1038/s41586-022-04975-9

Presentations

Canadian Cancer Research Conference. Canadian Cancer Research Alliance. Canada. November 2021. [oral]

The 15th Annual Lorne D. Sullivan Lectureship and Research Day. Department of Urologic Sciences, The University of British Columbia. Canada. June 2021. [oral]