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

Nat Genet
Authors
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.

Year of Publication
2016
Journal
Nat Genet
Volume
48
Issue
8
Pages
848-55
Date Published
2016 Aug
ISSN
1546-1718
DOI
10.1038/ng.3602
PubMed ID
27348297
PubMed Central ID
PMC4963271
Links
Grant list
F30 CA192725 / CA / NCI NIH HHS / United States
R01 CA188228 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States