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

Andrea Walens, Jiaxing Lin, Jeffrey S. Damrauer, Brock McKinney, Ryan Lupo, Rachel Newcomb, Douglas B. Fox, Nathaniel W. Mabe, Jeremy Gresham, Zhecheng Sheng, Alexander B. Sibley, Tristan De Buysscher, Hemant Kelkar, Piotr A. Mieczkowski, Kouros Owzar and James V. Alvarez ()
Additional contact information
Andrea Walens: Duke University
Jiaxing Lin: Duke University
Jeffrey S. Damrauer: Duke University
Brock McKinney: Duke University
Ryan Lupo: Duke University
Rachel Newcomb: Duke University
Douglas B. Fox: Duke University
Nathaniel W. Mabe: Duke University
Jeremy Gresham: Duke University
Zhecheng Sheng: Duke University
Alexander B. Sibley: Duke University
Tristan De Buysscher: University of North Carolina
Hemant Kelkar: University of North Carolina
Piotr A. Mieczkowski: University of North Carolina
Kouros Owzar: Duke University
James V. Alvarez: Duke University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18730-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18730-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18730-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().