(2016) Gibson, William; Hoivik, Erling A.; Halle, Mari K.; Taylor-Weiner, Amaro; Cherniack, Andrew D.; Berg, Anna; Holst, Frederik; Zack, Travis Ian; Werner, Henrica M. J.; Staby, Kjersti M.; Rosenberg, Mara; Stefansson, Ingunn M.; Kusonmano, Kanthida; Chevalier, Aaron; Mauland, Karen K.; Trovik, Jone; Krakstad, Camilla; Giannakis, Marios; Hodis, Eran; Woie, Kathrine; Bjorge, Line; Vintermyr, Olav K.; Wala, Jeremiah; Lawrence, Michael; Getz, Gad; Carter, Scott; Beroukhim, Rameen; Salvesen, Helga B.
Recent studies have detailed the genomic landscape of primary endometrial cancers, but their evolution 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 TCGA-data, identifying novel recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor NRIP1 in 12% of patients. We found that likely driver events tended to be shared by 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 within endometrial cancers and relative homogeneity across metastatic sites.
