Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence.

Journal Article (Journal Article)

The survival and recurrence of residual tumor cells following therapy constitutes one of the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how the clonal composition of tumors changes during relapse. We use cellular barcoding to monitor clonal dynamics during tumor recurrence in vivo. We find that clonal diversity decreases during tumor regression, residual disease, and recurrence. The recurrence of dormant residual cells follows several distinct routes. Approximately half of the recurrent tumors exhibit clonal dominance with a small number of subclones comprising the vast majority of the tumor; these clonal recurrences are frequently dependent upon Met gene amplification. A second group of recurrent tumors comprises thousands of subclones, has a clonal architecture similar to primary tumors, and is dependent upon the Jak/Stat pathway. Thus the regrowth of dormant tumors proceeds via multiple routes, producing recurrent tumors with distinct clonal composition, genetic alterations, and drug sensitivities.

Full Text

Duke Authors

Cited Authors

  • Walens, A; Lin, J; Damrauer, JS; McKinney, B; Lupo, R; Newcomb, R; Fox, DB; Mabe, NW; Gresham, J; Sheng, Z; Sibley, AB; De Buysscher, T; Kelkar, H; Mieczkowski, PA; Owzar, K; Alvarez, JV

Published Date

  • October 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 5017 -

PubMed ID

  • 33024122

Pubmed Central ID

  • PMC7539014

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-18730-z


  • eng