Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma

Werner-Klein M, Scheitler S, Hoffmann M, Hodak I, Dietz K, Lehnert P, Naimer V, Polzer B, Treitschke S, Werno C, Markiewicz A, Weidele K, Czyz Z, Hohenleutner U, Hafner C, Haferkamp S, Berneburg M, Ruemmele P, Ulmer A, Klein CA (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 9

Journal Issue: 1

DOI: 10.1038/s41467-017-02674-y

Abstract

Mouse models indicate that metastatic dissemination occurs extremely early; however, the timing in human cancers is unknown. We therefore determined the time point of metastatic seeding relative to tumour thickness and genomic alterations in melanoma. Here, we find that lymphatic dissemination occurs shortly after dermal invasion of the primary lesion at a median thickness of ~0.5 mm and that typical driver changes, including BRAF mutation and gained or lost regions comprising genes like MET or CDKNA2, are acquired within the lymph node at the time of colony formation. These changes define a colonisation signature that was linked to xenograft formation in immunodeficient mice and death from melanoma. Thus, melanoma cells leave primary tumours early and evolve at different sites in parallel. We propose a model of metastatic melanoma dormancy, evolution and colonisation that will inform direct monitoring of adjuvant therapy targets.

Additional Organisation(s)

Institute of Pathology

Involved external institutions

Universität Regensburg DE Germany (DE) Fraunhofer-Institut für Toxikologie und Experimentelle Medizin (ITEM) / Fraunhofer Institute for Toxicology and Experimental Medicine DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE)

How to cite

APA:

Werner-Klein, M., Scheitler, S., Hoffmann, M., Hodak, I., Dietz, K., Lehnert, P.,... Klein, C.A. (2018). Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma. Nature Communications, 9(1). https://doi.org/10.1038/s41467-017-02674-y

MLA:

Werner-Klein, Melanie, et al. "Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma." Nature Communications 9.1 (2018).

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