Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 128, Issue 4, Pages 1355-1370Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI96149
Keywords
-
Categories
Funding
- Marit and Hans Rausingg's Fund for Cancer Research
- Swedish Cancer Society
- Swedish Research Council-Starget-Linne
- Academy of Finland (Center of Excellence in Cancer Genetics Research)
- Finnish Cancer Foundations
- Sigrid Juselius Foundation
- Radiumhemmet
- KI-AZ Support Grant
- KI-Stockholm County Council
- Swedish Society for Medical Research (SSMF)
- Strategic Research Programme in Cancer (StratCan)
- Breast Cancer Theme Center (BRECT)
Ask authors/readers for more resources
Metastatic breast cancers are still incurable. Characterizing the evolutionary landscape of these cancers, including the role of metastatic axillary lymph nodes (ALNs) in seeding distant organ metastasis, can provide a rational basis for effective treatments. Here, we have described the genomic analyses of the primary tumors and metastatic lesions from 99 samples obtained from 20 patients with breast cancer. Our evolutionary analyses revealed diverse spreading and seeding patterns that govern tumor progression. Although linear evolution to successive metastatic sites was common, parallel evolution from the primary tumor to multiple distant sites was also evident. Metastatic spreading was frequently coupled with polyclonal seeding, in which multiple metastatic subclones originated from the primary tumor and/or other distant metastases. Synchronous ALN metastasis, a well-established prognosticator of breast cancer, was not involved in seeding the distant metastasis, suggesting a hematogenous route for cancer dissemination. Clonal evolution coincided frequently with emerging driver alterations and evolving mutational processes, notably an increase in apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like-associated (APOBEC-associated) mutagenesis. Our data provide genomic evidence for a role of ALN metastasis in seeding distant organ metastasis and elucidate the evolving mutational landscape during cancer progression.
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