GRCh38 · COSMIC v92

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Clonal evolution of high-grade serous ovarian carcinoma from primary to recurrent disease.
Paper ID
COSP29755
Authors
Castellarin M, Milne K, Zeng T, Tse K, Mayo M, Zhao Y, Webb JR, Watson PH, Nelson BH and Holt RA
Affiliation
BC Cancer Agency, Michael Smith Genome Sciences Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3 Canada; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Journal
The Journal of pathology, 2012
ISSN: 1096-9896
PMID: 22996961 (view at PubMed or Europe PMC)
Abstract
High-grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumors are highly sensitive to cytoreductive surgery and platinum- and taxane-based chemotherapy, the majority of patients experience recurrence of treatment-resistant tumors. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumor cells harvested from ascites at three time points (primary, first recurrence and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumors were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumors from all three patients also harbored mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumors were present in primary tumors. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumor with negligible accumulation of new mutations during standard treatment. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Paper Status
Curated