Journal
SCIENCE
Volume 357, Issue 6346, Pages 55-60Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aai8515
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Funding
- Department of Defense [W81XWH-10-0016, W81XWH-12-1-0362, W81XWH-15-1-0579]
- National Human Genome Research Institute [U54 HG007963]
- National Cancer Institute [P01-CA080124, R35-CA19//43]
- Francis Crick Institute [FC001169]
- Austrian Science Fund [J-3996]
- National Foundation for Cancer Research
- Ludwig Center at Harvard
- MRC [MR/P014712/1] Funding Source: UKRI
- Cancer Research UK [17786, 19310, 20466] Funding Source: researchfish
- Medical Research Council [MR/P014712/1] Funding Source: researchfish
- Rosetrees Trust [M391, M179, M640, M445, M231-CD1] Funding Source: researchfish
- The Francis Crick Institute [10359, C60895/A23896, 10174, 10467, 10172, 10170, VEG 108844, A1278, C28575/A25223, 10169, 10485] Funding Source: researchfish
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The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.
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