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Series GSE40546 Query DataSets for GSE40546
Status Public on Oct 01, 2014
Title CTCR-OV03/CTCR-OV04 ovarian cancer
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary High-grade serous ovarian cancer (HGSOC) exhibits significant genomic heterogeneity within a patient at presentation. Recent work has suggested that this heterogeneity is linked to the development of resistance and disease progression in that chemotherapy selects for minor resistant subclones embodied in presentation disease leading to short progression-free survival and resistant relapse. Cell line models support this by showing that relapse is not an immediate descendant of presentation disease, but so far no immediate clinical evidence has been provided that convincingly demonstrates the origin of relapse. It is further still unclear what evolutionary processes shape the mutational landscape of HGSOC in vivo and to what extent the degree of genomic heterogeneity impacts a patient's clinical outcome. We address these questions by inferring evolutionary trees of metastatic disease from structural variations between 138 cancer samples obtained from 17 patients undergoing neoadjuvant chemotherapy for HGSOC. Using novel phylogenetic methods, we quantify genomic changes in the course of chemotherapy and the degree of clonal expansion and show that these indices determine patient outcome with high accuracy. We demonstrate that relapse is indeed a minor subclone of presentation disease by verifying that the focal NF1 deletion of a relapse case was already present at biopsy. By leveraging the information contained in the evolutionary trees, we unveil the etiology of genetic heterogeneity and the tumorigenic potential of HGSOC cell populations.
This is the first comprehensive study showing the origin, strength and effect of genetic heterogeneity in HGSOC in a clinical setting. In addition to its immediate clinical significance, it strengthens previous statements that single sample biopsies are seemingly insufficient to predict disease progression and stresses the importance of establishing multiple sampling as a routine approach in the clinic.
Overall design Clinical data and tissue samples were collected on the prospective CTCR-OV03 and CTCR-OV04 clinical studies designed to identify biomarkers of heterogeneity.
Contributor(s) Ng CK, Cooke SL, Brenton JD
Citation(s) 25710373, 24743184
Submission date Aug 31, 2012
Last update date Oct 23, 2019
Contact name Charlotte K Y Ng
Organization name University Hospital Basel
Department Pathology
Street address Schönbeinstrasse 40
City Basel
ZIP/Postal code 4003
Country Switzerland
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (138)
GSM996044 OV03-04_Om_S01
GSM996045 OV03-04_Om_S02
GSM996046 OV03-01_Om_S03
BioProject PRJNA174252

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40546_PICNIC_output_data.txt.gz 14.6 Mb (ftp)(http) TXT
GSE40546_RAW.tar 3.5 Gb (http)(custom) TAR (of CEL)
Processed data are available on Series record

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