Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02674-y
Keywords
-
Categories
Funding
- University of Tubingen [IZKF-1686-0-0]
- Ludwig-Hiermaier-Stiftung
- Wilhelm-Sander Stiftung [2003.005, 2015-016.1]
- Deutsche Krebshilfe [108008]
- Dr Josef Steiner Cancer foundation
- ERC [322602]
- DFG [WE 4632/1-1, WE 4632/4-1, KL 1233/14-1]
- DFG
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available