Need Help?

Distinct evolutionary trajectories of primary high grade serous ovarian cancers revealed through spatial mutational profiling

High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to the emergence of treatment-resistant subclones. We sought to measure the degree of genomic diversity within primary, untreated HGSCs to examine the natural state of tumour evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated HGSC tumour specimens (six patients), including ovarian masses, distant metastases and fallopian tube lesions. We found widespread intratumoural variation in mutation, copy number and gene expression profiles, with key driver alterations in genes present in only a subset of samples (eg PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range 10.2 to 91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole-genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology, with common aetiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating that diversity arises at early stages of tumourigenesis. Our results revealed that HGSCs exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug-resistance mechanisms

Request Access

BC Cancer, part of the Provincial Health Services Authority - Data Access Policy

Access to this data is controlled. There are a number of steps that a researcher must take to obtain access to this data, including execution of a Data Access Agreement between the institutions. The process is overseen by the Technology Development Office; please contact our general email address Please only click the "request data" button on the EGA website after a Data Access Agreement is fully executed.

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001000547 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00000238571 bam 5.0 GB
EGAF00000238572 bam 9.2 GB
EGAF00000238573 bam 14.4 GB
EGAF00000238574 bam 8.9 GB
EGAF00000238575 bam 7.1 GB
EGAF00000238576 bam 7.2 GB
EGAF00000238577 bam 6.8 GB
EGAF00000238578 bam 6.9 GB
EGAF00000238579 bam 8.9 GB
EGAF00000238580 bam 16.7 GB
EGAF00000238581 bam 12.2 GB
EGAF00000238582 bam 22.9 GB
EGAF00000238583 bam 11.9 GB
EGAF00000238584 bam 9.7 GB
EGAF00000238585 bam 7.5 GB
EGAF00000238586 bam 7.2 GB
EGAF00000238587 bam 7.9 GB
EGAF00000238588 bam 6.3 GB
EGAF00000238589 bam 7.9 GB
EGAF00000238590 bam 7.7 GB
EGAF00000238591 bam 9.0 GB
EGAF00000238592 bam 8.5 GB
EGAF00000238593 bam 11.2 GB
EGAF00000238594 bam 9.2 GB
EGAF00000238595 bam 9.6 GB
25 Files (240.0 GB)