Werner-Klein, Melanie and Scheitler, Sebastian and Hoffmann, Martin and Hodak, Isabelle and Dietz, Klaus and Lehnert, Petra and Naimer, Veronika and Polzer, Bernhard and Treitschke, Steffi and Werno, Christian and Markiewicz, Aleksandra and Weidele, Kathrin and Czyz, Zbigniew and Hohenleutner, Ulrich and Hafner, Christian and Haferkamp, Sebastian and Berneburg, Mark and Ruemmele, Petra and Ulmer, Anja and Klein, Christoph A. (2018) Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma. NATURE COMMUNICATIONS, 9: 595. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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 similar to 0.5mm 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPARATIVE GENOMIC HYBRIDIZATION; MINIMAL RESIDUAL CANCER; CELL SEQUENCING DATA; CUTANEOUS MELANOMA; BREAST-CANCER; MUTATION FREQUENCIES; ONCOGENIC MUTATIONS; EARLY DISSEMINATION; BRANCHED EVOLUTION; EQUIVALENCE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2020 09:55 |
| Last Modified: | 18 Mar 2020 09:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15051 |
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