Multiplex Functional Interrogation of Oncogenic Networks in Bladder Cancer
Abstract
In this reporting period, additional tumors were generated using the mouse urothelial organoid transformation assay using barcoded lentiviral pools. In this system, single cell DNA amplicon sequencing resolves clonal architecture in the tumors but does not allow in situ association with cancer histologies. A workflow of laser capture microdissection of stained tissue sections and DNA amplicon sequencing was established to overcome this issue. Tumor models of histologic variants of bladder cancer were analyzed and lentiviral bar-codes numerated to identify the putative genetic alterations associated with each. Validation studies to re-generate these tumors and leave-one-out analyses to examine the role of each genetic alteration in cancer initiation/phenotype are ongoing. Lastly, lentiviral transduction of mouse urothelial cells in organoid culture was found to follow a (non-skewed)binomial distribution which supports the potential for co-occurrence and mutual exclusivity analyses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1150354
Entities
People
- John K Lee
Organizations
- Fred Hutchinson Cancer Center