Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer

Serio, Ryan N, Scheben, Armin, Lu, Billy, Gargiulo, Domenic V, Patruno, Lucrezia, Buckholtz, Caroline L, Chaffee, Ryan J, Jibilian, Megan C, Persaud, Steven G, Staklinski, Stephen J, Hassett, Rebecca, Brault, Lise M, Ramazzotti, Daniele, Barbieri, Christopher E, Siepel, Adam C, Nowak, Dawid G (July 2024) Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer. Cancer Discovery. ISSN 2159-8274

Abstract

The patterns by which primary tumors spread to metastatic sites remain poorly understood. Here, we define patterns of metastatic seeding in prostate cancer (PCa) using a novel injection-based mouse model - EvoCaP (Evolution in Cancer of the Prostate), featuring aggressive metastatic cancer to bone, liver, lungs, and lymph nodes. To define migration histories between primary and metastatic sites, we used our EvoTraceR pipeline to track distinct tumor clones containing recordable barcodes. We detected widespread intratumoral heterogeneity from the primary tumor in metastatic seeding, with few clonal populations (CPs) instigating most migration. Metastasis-to-metastasis seeding was uncommon, as most cells remained confined within the tissue. Migration patterns in our model were congruent with human PCa seeding topologies. Our findings support the view of metastatic PCa as a systemic disease driven by waves of aggressive clones expanding their niche, infrequently overcoming constraints that otherwise keep them confined in the primary or metastatic site.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > cancer types > prostate cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics and Genomics Program
CSHL labs > Siepel lab
CSHL Cancer Center Program
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 5 July 2024
Date Deposited: 08 Jul 2024 13:11
Last Modified: 08 Jul 2024 13:11
Related URLs:
URI: https://repository.cshl.edu/id/eprint/41596

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