Journal Article

Origins of lymphatic and distant metastases in human colorectal cancer

Brachtel, Elena, van de Wetering, Marc, Reiter, Johannes G., Clevers, Hans, Rowan, Andrew, Cai, Tianxi, Nowak, Martin A., Naxerova, Kamila, Elledge, Stephen J., Swanton, Charles, Lennerz, Jochen K., Jain, Rakesh K.

2017

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: 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