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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 emergence of treatment-resistant sub-clones. We sought to measure the degree of genomic diversity within primary, untreated HGSC to examine the natural state of tumor evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on thirty-one spatially and temporally separated HGSC tumor specimens (six patients) including ovarian masses, distant metastases, and fallopian tube lesions. We found widespread intra-tumoral variation in mutation, copy number, and gene expression profiles, with key driver alterations in genes present in only a subset of samples (e.g. 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 etiologic 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 diversity arises at early stages of tumorigenesis. Our results reveal that HGSC 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.

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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
EGAF00000590846 bam 77.2 GB
EGAF00000590847 bam 81.9 GB
EGAF00000590848 bam 77.0 GB
EGAF00000590849 bam 65.7 GB
EGAF00000590850 bam 66.5 GB
EGAF00000590851 bam 66.9 GB
EGAF00000590852 bam 67.2 GB
EGAF00000590853 bam 67.4 GB
EGAF00000590854 bam 160.7 GB
EGAF00000590855 bam 156.5 GB
EGAF00000590856 bam 144.7 GB
EGAF00000590857 bam 167.9 GB
EGAF00000590858 bam 161.1 GB
EGAF00000590859 bam 149.2 GB
EGAF00000590860 bam 172.4 GB
EGAF00000590861 bam 144.8 GB
EGAF00000590862 bam 168.2 GB
EGAF00000590863 bam 156.3 GB
EGAF00000590864 bam 238.6 GB
EGAF00000590865 bam 226.4 GB
EGAF00000590866 bam 249.8 GB
EGAF00000590867 bam 222.6 GB
EGAF00000590868 bam 246.1 GB
EGAF00000590869 bam 233.9 GB
EGAF00000590870 bam 227.1 GB
EGAF00000590871 bam 250.6 GB
EGAF00000590872 bam 238.4 GB
EGAF00000590873 bam 234.6 GB
EGAF00000590874 bam 8.9 MB
EGAF00000590875 bam 9.9 MB
EGAF00000590876 bam 1.9 MB
EGAF00000590877 bam 25.7 MB
EGAF00000590878 bam 15.4 MB
EGAF00000590879 bam 4.3 MB
EGAF00000590880 bam 21.7 MB
EGAF00000590881 bam 20.6 MB
EGAF00000590882 bam 19.8 MB
EGAF00000590883 bam 4.8 MB
EGAF00000590884 bam 4.1 MB
EGAF00000590885 bam 41.4 MB
EGAF00000590886 bam 20.4 MB
EGAF00000590887 bam 11.3 MB
EGAF00000590888 bam 20.3 MB
EGAF00000590889 bam 6.0 MB
EGAF00000590890 bam 38.7 MB
EGAF00000590891 bam 14.2 MB
EGAF00000590892 bam 26.1 MB
EGAF00000590893 bam 6.0 MB
EGAF00000590894 bam 6.9 MB
EGAF00000590895 bam 49.0 MB
EGAF00000590896 bam 33.9 MB
EGAF00000590897 bam 36.7 MB
EGAF00000590898 bam 16.4 MB
EGAF00000590899 bam 36.4 MB
EGAF00000590900 bam 26.8 MB
EGAF00000590901 bam 3.8 MB
EGAF00000590902 bam 3.6 MB
EGAF00000590903 bam 65.7 MB
EGAF00000590904 bam 30.6 MB
EGAF00000590905 bam 5.5 MB
EGAF00000590906 bam 4.3 MB
EGAF00000590907 bam 23.0 MB
EGAF00000590908 bam 36.0 MB
EGAF00000590909 bam 4.4 MB
EGAF00000590910 bam 23.8 MB
EGAF00000590911 bam 11.4 MB
EGAF00000590912 bam 44.7 MB
EGAF00000590913 bam 6.2 MB
EGAF00000590914 bam 5.1 MB
EGAF00000590915 bam 31.8 MB
EGAF00000590916 bam 3.4 MB
EGAF00000590917 bam 4.2 MB
EGAF00000590918 bam 5.3 MB
EGAF00000590919 bam 5.8 MB
EGAF00000590920 bam 49.4 MB
EGAF00000590921 bam 40.1 MB
EGAF00000590922 bam 5.2 MB
EGAF00000590923 bam 31.4 MB
EGAF00000590924 bam 3.8 MB
EGAF00000590925 bam 4.3 MB
EGAF00000590926 bam 5.2 MB
EGAF00000590927 bam 4.3 MB
EGAF00000590928 bam 5.9 MB
EGAF00000590929 bam 5.1 MB
EGAF00000590930 bam 62.7 MB
EGAF00000590931 bam 50.1 MB
EGAF00000590932 bam 54.9 MB
EGAF00000590933 bam 41.7 MB
EGAF00000590934 bam 5.3 MB
EGAF00000590935 bam 4.2 MB
EGAF00000590936 bam 88.2 GB
EGAF00000590937 bam 86.0 GB
EGAF00000590938 bam 62.8 GB
EGAF00000590939 bam 63.8 GB
EGAF00000590940 bam 64.7 GB
EGAF00000590941 bam 65.4 GB
EGAF00000590942 bam 66.0 GB
EGAF00000590943 bam 12.3 MB
EGAF00000590944 bam 4.2 MB
EGAF00000590945 bam 9.7 MB
EGAF00000590946 bam 57.3 MB
EGAF00000590947 bam 15.1 MB
EGAF00000590948 bam 32.4 MB
EGAF00000590949 bam 4.0 MB
EGAF00000590950 bam 9.6 MB
EGAF00000590951 bam 5.4 MB
EGAF00000590952 bam 7.9 MB
EGAF00000590953 bam 4.1 MB
EGAF00000590954 bam 5.3 MB
EGAF00000590955 bam 41.8 MB
EGAF00000590956 bam 35.8 MB
EGAF00000590957 bam 3.5 MB
EGAF00000590958 bam 3.2 MB
EGAF00000590959 bam 6.1 MB
EGAF00000590960 bam 4.5 MB
EGAF00000590961 bam 53.4 MB
EGAF00000590962 bam 30.3 MB
EGAF00000590963 bam 4.2 MB
EGAF00000590964 bam 11.0 MB
EGAF00000590965 bam 35.3 MB
EGAF00000590966 bam 4.6 MB
EGAF00000590967 bam 23.9 MB
EGAF00000590968 bam 28.1 MB
EGAF00000590969 bam 509.5 kB
EGAF00000590970 bam 4.7 MB
EGAF00000590971 bam 3.1 MB
EGAF00000590972 bam 5.0 MB
EGAF00000590973 bam 5.6 MB
EGAF00000590974 bam 5.1 MB
EGAF00000590975 bam 29.9 MB
EGAF00000590976 bam 7.6 MB
131 Files (5.0 TB)