Origins of lymphatic and distant metastases in human colorectal cancer

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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)55-60
Number of pages6
JournalScience
Volume357
Issue number6346
DOIs
Publication statusPublished - 07 Jul 2017

Keywords

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

Fingerprint

Dive into the research topics of 'Origins of lymphatic and distant metastases in human colorectal cancer'. Together they form a unique fingerprint.

Cite this