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Nat Genet. 2016 Aug;48(8):848-55. doi: 10.1038/ng.3602. Epub 2016 Jun 27.

The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis.

Author information

1
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
2
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
4
Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
5
Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.
6
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
7
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
8
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
9
Computational Biology Unit, University of Bergen, Bergen, Norway.
10
Present address: Bioinformatics and Systems Biology Program, Computational Biology Unit, School of Bioresources and Technology, King Mongkut's University of Technology, Thonburi, Bangkok, Thailand.
11
Department of Biomedicine, University of Bergen, Bergen, Norway.
12
Joint Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Broad Institute, Boston, Massachusetts, USA.
13
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
14
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Abstract

Recent studies have detailed the genomic landscape of primary endometrial cancers, but the evolution of these cancers into metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed The Cancer Genome Atlas (TCGA) data, identifying new recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor gene NRIP1 in 12% of patients. We found that likely driver events were present in both primary and metastatic tissue samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses indicated that the sampled metastases typically arose from a common ancestral subclone that was not detected in the primary tumor biopsy. These data demonstrate extensive genetic heterogeneity in endometrial cancers and relative homogeneity across metastatic sites.

PMID:
27348297
PMCID:
PMC4963271
DOI:
10.1038/ng.3602
[Indexed for MEDLINE]
Free PMC Article

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