The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis
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Author list: Gibson W.J., Hoivik E.A., Halle M.K., Taylor-Weiner A., Cherniack A.D., Berg A., Holst F., Zack T.I., Werner H.M.J., Staby K.M., Rosenberg M., Stefansson I.M., Kusonmano K., Chevalier A., Mauland K.K., Trovik J., Krakstad C., Giannakis M., Hodis E., Woie K., Bjorge L., Vintermyr O.K., Wala J.A., Lawrence M.S., Getz G., Carter S.L., Beroukhim R., Salvesen H.B.
Publisher: Nature Research
Publication year: 2016
Journal: Nature Genetics (1061-4036)
Volume number: 48
Issue number: 8
Start page: 848
End page: 855
Number of pages: 8
ISSN: 1061-4036
eISSN: 1546-1718
Languages: English-Great Britain (EN-GB)
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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. ฉ 2016 Nature America, Inc. All rights reserved.
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