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Adaptation and selection shape clonal evolution of tumors during residual disease and recurrence
- Source :
- Nature Communications, Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020)
- Publication Year :
- 2019
-
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.<br />The cellular composition of recurrent tumors can provide insight into resistance to therapy and inform on second line therapies. Here, using a genetically modified mouse, the authors perform barcoding experiments of the primary tumors to allow them to study the clonal dynamics of tumor recurrence.
- Subjects :
- 0301 basic medicine
Epithelial-Mesenchymal Transition
Lung Neoplasms
Receptor, ErbB-2
Science
Tumour heterogeneity
General Physics and Astronomy
Mice, Nude
Tumor cells
Breast Neoplasms
Disease
Biology
Somatic evolution in cancer
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
0302 clinical medicine
Breast cancer
Crizotinib
Cell Line, Tumor
medicine
Animals
Humans
lcsh:Science
Clonal diversity
Dominance (genetics)
Multidisciplinary
Clonal architecture
High-Throughput Nucleotide Sequencing
General Chemistry
Proto-Oncogene Proteins c-met
medicine.disease
Xenograft Model Antitumor Assays
Tumor recurrence
Gene Expression Regulation, Neoplastic
030104 developmental biology
030220 oncology & carcinogenesis
Doxycycline
Cancer research
lcsh:Q
Female
Neoplasm Recurrence, Local
Single-Cell Analysis
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....2ec100826d6dbb32fe10bb9a2b48d1e0