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Nat Commun. 2018 May 4;9(1):1793. doi: 10.1038/s41467-018-04278-6.

Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis.

Author information

1
Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, 60637, USA.
2
Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, 60637, USA.
3
Center for Research Informatics, The University of Chicago, Chicago, IL, 60637, USA.
4
Department of Surgery, The University of Chicago, Chicago, IL, 60637, USA.
5
Department of Surgery, Southern Illinois University, Springfield, IL, 62702, USA.
6
Department of Pathology, NorthShore University Hospital, Evanston, IL, 60201, USA.
7
Institute for Genomics and Systems Biology, The University of Chicago, Chicago, IL, 60637, USA.
8
Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA.
9
Department of Surgery, Yale School of Medicine, New Haven, CT, 06510, USA.
10
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
11
Department of Surgery, NorthShore University Hospital, Evanston, IL, 60201, USA.
12
Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, 60637, USA. rrw@radonc.uchicago.edu.
13
Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, 60637, USA. rrw@radonc.uchicago.edu.

Abstract

The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases are limited in extent and curable with focal therapies. A subset of patients with metastatic colorectal cancer achieves prolonged survival after resection of liver metastases consistent with oligometastasis. Here we define three robust subtypes of de novo colorectal liver metastasis through integrative molecular analysis. Patients with metastases exhibiting MSI-independent immune activation experience the most favorable survival. Subtypes with adverse outcomes demonstrate VEGFA amplification in concert with (i) stromal, mesenchymal, and angiogenic signatures, or (ii) exclusive NOTCH1 and PIK3C2B mutations with E2F/MYC activation. Molecular subtypes complement clinical risk stratification to distinguish low-risk, intermediate-risk, and high-risk patients with 10-year overall survivals of 94%, 45%, and 19%, respectively. Our findings provide a framework for integrated classification and treatment of metastasis and support the biological basis of curable oligometastatic colorectal cancer. These concepts may be applicable to many patients with metastatic cancer.

PMID:
29728604
PMCID:
PMC5935683
DOI:
10.1038/s41467-018-04278-6
[Indexed for MEDLINE]
Free PMC Article

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