BBB seminar: Erling Andre Høivik
Genomic analysis of paired endometrial cancer primaries and metastases
Erling Andre Høivik
Department of Clinical Science, University of Bergen
Formation of metastases is the major cause of cancer related deaths, and targeting metastases remains a key challenge in cancer management. While recent efforts, such as that performed by The Cancer Genome Atlas (TCGA) consortium, have provided detailed insight into the genomic landscape of primary endometrial cancers, the genomic evolution of these cancers towards metastases has been less characterized. We have performed whole-exome sequencing of biopsies ranging from endometrial hyperplasias to primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We have expanded and reanalyzed TCGA data, and added new significantly mutated genes to the catalogue of mutations in primary endometrial cancer, such as NRIP1 (nuclear receptor-interacting protein 1), a cofactor for the estrogen receptor. While driver mutations were typically shared by the primary tumor and metastases, we found overall extensive genetic heterogeneity in endometrial cancers and relative homogeneity across metastatic sites. Phylogenetic analyses indicated that typically metastasis arises from a common ancestral subclone of the primary tumor.
Gibson WJ, Hoivik EA, (…) Salvesen HB. 2016. The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis. Nat Genet 48:848-55.
Chairperson: Marit Bakke, Department of Biomedicine