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Cell Rep. 2018 Nov 20;25(8):2208-2222.e7. doi: 10.1016/j.celrep.2018.10.090.

Cellular Barcoding Identifies Clonal Substitution as a Hallmark of Local Recurrence in a Surgical Model of Head and Neck Squamous Cell Carcinoma.

Author information

1
Department of Otolaryngology - Head and Neck Surgery, University Hospital of Lausanne, Lausanne, Switzerland.
2
Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
3
Clinical and Biomedical Proteomics Group, Cancer Research UK Centre, Leeds Institute of Cancer and Pathology, St. James's University Hospital, Leeds, UK.
4
Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustave Carus, Technische Universität Dresden, Dresden, Germany.
5
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
6
German Cancer Consortium (DKTK), Translational Radiation Oncology, German Cancer Research Center (DKFZ), Core Center Heidelberg, Heidelberg, Germany; Division of Molecular and Translational Radiation Oncology, Heidelberg University Hospital (UKHD) and DKFZ, Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany.
7
Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. Electronic address: fehse@uke.de.
8
Department of Otolaryngology - Head and Neck Surgery, University Hospital of Lausanne, Lausanne, Switzerland. Electronic address: christian.simon@chuv.ch.
9
Department of Otolaryngology - Head and Neck Surgery, University Hospital of Lausanne, Lausanne, Switzerland. Electronic address: genrich.tolstonog@chuv.ch.

Abstract

Local recurrence after surgery for head and neck squamous cell carcinoma (HNSCC) remains a common event associated with a dismal prognosis. Improving this outcome requires a better understanding of cancer cell populations that expand from postsurgical minimal residual disease (MRD). Therefore, we assessed clonal dynamics in a surgical model of barcoded HNSCC growing in the submental region of immunodeficient mice. Clonal substitution and massive reduction of clonal heterogeneity emerged as hallmarks of local recurrence, as the clones dominating in less heterogeneous recurrences were scarce in their matched primary tumors. These lineages were selected by their ability to persist after surgery and competitively expand from MRD. Clones enriched in recurrences exhibited both private and shared genetic features and likely originated from ancestors shared with clones dominating in primary tumors. They demonstrated high invasiveness and epithelial-to-mesenchymal transition, eventually providing an attractive target for obtaining better local control for these tumors.

KEYWORDS:

DNA barcoding; LeGO vectors; RGB marking; clonal heterogeneity; clonal substitution; epithelial-mesenchymal transition; head and neck squamous cell carcinoma; invasion; recurrent tumor-initiating clones

PMID:
30463016
DOI:
10.1016/j.celrep.2018.10.090
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