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

Publication ,  Journal Article
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 ...
Published in: Nat Commun
October 6, 2020

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 6, 2020

Volume

11

Issue

1

Start / End Page

5017

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Single-Cell Analysis
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-met
  • Neoplasm Recurrence, Local
  • Mice, Nude
  • Lung Neoplasms
  • Humans
  • High-Throughput Nucleotide Sequencing
 

Citation

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Walens, A., Lin, J., Damrauer, J. S., McKinney, B., Lupo, R., Newcomb, R., … Alvarez, J. V. (2020). Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence. Nat Commun, 11(1), 5017. https://doi.org/10.1038/s41467-020-18730-z
Walens, Andrea, Jiaxing Lin, Jeffrey S. Damrauer, Brock McKinney, Ryan Lupo, Rachel Newcomb, Douglas B. Fox, et al. “Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence.Nat Commun 11, no. 1 (October 6, 2020): 5017. https://doi.org/10.1038/s41467-020-18730-z.
Walens A, Lin J, Damrauer JS, McKinney B, Lupo R, Newcomb R, et al. Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence. Nat Commun. 2020 Oct 6;11(1):5017.
Walens, Andrea, et al. “Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence.Nat Commun, vol. 11, no. 1, Oct. 2020, p. 5017. Pubmed, doi:10.1038/s41467-020-18730-z.
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. Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence. Nat Commun. 2020 Oct 6;11(1):5017.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 6, 2020

Volume

11

Issue

1

Start / End Page

5017

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Single-Cell Analysis
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-met
  • Neoplasm Recurrence, Local
  • Mice, Nude
  • Lung Neoplasms
  • Humans
  • High-Throughput Nucleotide Sequencing