Origins of Lymphatic and Distant Metastases in Human Colorectal Cancer

Overview

Journal Science

Specialty Science

Date 2017 Jul 8

PMID 28684519

Citations 245

Authors

Kamila Naxerova

Johannes G Reiter

Elena Brachtel

Jochen K Lennerz

Marc van de Wetering

Andrew Rowan

Tianxi Cai

Hans Clevers

Charles Swanton

Martin A Nowak

Stephen J Elledge

Rakesh K Jain

Affiliations

Soon will be listed here.

Abstract

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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