Lineage-Coupled Clonal Capture Identifies Clonal Evolution Mechanisms and Vulnerabilities of BRAFV600E Inhibition Resistance in Melanoma

Authors

Ze-Yan Zhang
Yingwen Ding
Ravesanker Ezhilarasan
Tenzin Lhakhang
Qianghu Wang
Jie Yang
Aram S Modrek
Hua Zhang
Aristotelis Tsirigos
Andrew Futreal
Giulio F Draetta
Roel G W Verhaak
Erik P Sulman

Publication Date

10-6-2022

Journal

Cell Discovery

Abstract

Targeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed "CAPTURE", a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRAF

Keywords

Melanoma, Tumour heterogeneity

Comments

Supplementary Material

PMID: 36202798

DOI

10.1038/s41421-022-00462-7

PMID

36202798

PMCID

PMC9537441

PubMedCentral® Posted Date

October 2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes