Origins of lymphatic and distant metastases in human colorectal cancer

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 sys...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2017-07, Vol.357 (6346), p.55-60
Main Authors: Naxerova, Kamila, Reiter, Johannes G., Brachtel, Elena, Lennerz, Jochen K., van de Wetering, Marc, Rowan, Andrew, Cai, Tianxi, Clevers, Hans, Swanton, Charles, Nowak, Martin A., Elledge, Stephen J., Jain, Rakesh K.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biopsy
Cancer
Child
Child, Preschool
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - classification
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Deoxyribonucleic acid
DNA
DNA - genetics
Humans
INDEL Mutation
Lymph nodes
Lymph Nodes - pathology
Lymphatic Metastasis
Lymphatic system
Mastectomy
Metastases
Metastasis
Models, Biological
Neoplasm Staging
Organs
Patients
Phylogenetics
Phylogeny
Prognosis
Tumors
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aai8515