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

Study ID	Alternative Stable ID	Type
EGAS00001000547		Other

Study ID

Alternative Stable ID

Type

EGAS00001000547

Other

Study Description

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.

(Show Less)

Dataset ID	Description	Technology	Samples
EGAD00001000669	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 ... (Show More) 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, CTN... (Read more)	Illumina Genome Analyzer	25
EGAD00001000974	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) ... (Show More) 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... (Read more)	Illumina HiSeq 2000,Illumina MiSeq	131
EGAD00001000978	Multi-region whole genome sequencing of an high grade serous ovarian carcinoma sample for characterization of genomic intra-tumoural heterogeneity. Multi-region whole genome sequencing of an high grade serous ovarian carcinoma sample for characterization of genomic intra-tumoural heterogeneity.	Illumina HiSeq 2000	48
EGAD00010000500	Case samples using U133 Plus 2.0 Array Case samples using U133 Plus 2.0 Array	Affymetrix_U133plus2-	35
EGAD00010000502	Case samples using SNP Array 6.0 Case samples using SNP Array 6.0	Affymetrix_U133plus2-	35
EGAD00010000504	Control samples using SNP Array 6.0 Control samples using SNP Array 6.0	Affymetrix_U133plus2-	35

Dataset ID

Description

Technology

Samples

EGAD00001000669

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 ... (Show More)

Illumina Genome Analyzer

EGAD00001000974

Illumina HiSeq 2000,Illumina MiSeq

131

EGAD00001000978

Multi-region whole genome sequencing of an high grade serous ovarian carcinoma sample for characterization of genomic intra-tumoural heterogeneity.

Illumina HiSeq 2000

EGAD00010000500

Case samples using U133 Plus 2.0 Array

Affymetrix_U133plus2-

EGAD00010000502

Case samples using SNP Array 6.0