title: The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis.
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.
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Gibson
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Erling A
authors.initials: EA
authors.lastname: Hoivik
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Mari K
authors.initials: MK
authors.lastname: Halle
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Amaro
authors.initials: A
authors.lastname: Taylor-Weiner
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cherniack
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Anna
authors.initials: A
authors.lastname: Berg
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Frederik
authors.identifier: 0000-0002-5928-2175
authors.initials: F
authors.lastname: Holst
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Travis I
authors.initials: TI
authors.lastname: Zack
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Henrica M J
authors.initials: HM
authors.lastname: Werner
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjersti M
authors.initials: KM
authors.lastname: Staby
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Mara
authors.initials: M
authors.lastname: Rosenberg
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stefansson
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Computational Biology Unit, University of Bergen, Bergen, Norway.|Present address: Bioinformatics and Systems Biology Program, Computational Biology Unit, School of Bioresources and Technology, King Mongkut's University of Technology, Thonburi, Bangkok, Thailand.
authors.forename: Kanthida
authors.initials: K
authors.lastname: Kusonmano
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Chevalier
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Mauland
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Jone
authors.identifier: 0000-0002-3808-6407
authors.initials: J
authors.lastname: Trovik
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Krakstad
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Marios
authors.initials: M
authors.lastname: Giannakis
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Hodis
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.
authors.forename: Kathrine
authors.initials: K
authors.lastname: Woie
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Line
authors.initials: L
authors.lastname: Bjorge
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Olav K
authors.initials: OK
authors.lastname: Vintermyr
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jeremiah A
authors.initials: JA
authors.lastname: Wala
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Joint Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Broad Institute, Boston, Massachusetts, USA.|Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Carter
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.affiliation: Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
mesh_terms: D000008:Abdominal Neoplasms / Q000235:genetics* / Q000556:secondary; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D004714:Endometrial Hyperplasia / Q000235:genetics* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D019143:Evolution, Molecular; D059472:Exome / Q000235:genetics; D005260:Female; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010386:Pelvic Neoplasms / Q000235:genetics* / Q000556:secondary; D010802:Phylogeny
chemical_list: D014408:Biomarkers, Tumor