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Origins of lymphatic and distant metastases in human colorectal cancer

Naxerova, K; Reiter, JG; Brachtel, E; Lennerz, JK; van de Wetering, M; Rowan, A; Cai, T; ... Jain, RK; + view all (2017) Origins of lymphatic and distant metastases in human colorectal cancer. Science , 357 (6346) pp. 55-60. 10.1126/science.aai8515. Green open access

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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.

Type: Article
Title: Origins of lymphatic and distant metastases in human colorectal cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.aai8515
Publisher version: http://dx.doi.org/10.1126/science.aai8515
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10055860
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