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Science. 2017 Jul 7;357(6346):55-60. doi: 10.1126/science.aai8515.

Origins of lymphatic and distant metastases in human colorectal cancer.

Author information

1
Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. naxerova.kamila@mgh.harvard.edu.
2
Division of Genetics, Department of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
3
Program for Evolutionary Dynamics, Harvard University, Cambridge, MA 02138, USA.
4
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
5
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, 3584CT Utrecht, Netherlands.
6
Cancer Genomics Netherlands, UMC Utrecht, 3584CG Utrecht, Netherlands.
7
The Francis Crick Institute, London NW1 1AT, UK.
8
Department of Biostatistics, Harvard University, Boston, MA 02115, USA.
9
University College London Cancer Institute, London WC1E 6DD, UK.
10
Department of Mathematics and Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
11
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
12
Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

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.

PMID:
28684519
PMCID:
PMC5536201
DOI:
10.1126/science.aai8515
[Indexed for MEDLINE]
Free PMC Article

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