Search Results - EGA European Genome-Phenome Archive

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.

Dataset EGAD00001000974

12213 results for "cancer rna-seq"

in 24.88 milliseconds.

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

Genome and transcriptome sequence data from a metastatic breast carcinoma patient

Genome and transcriptome sequence data from a squamous cell carcinoma of vulva patient

Genome and transcriptome sequence data from a vulvar metastatic melanoma patient

Genome and transcriptome sequence data from a squamous cell carcinoma of anal canal patient

Genome and transcriptome sequence data from a right breast carcinoma patient

Genome and transcriptome sequence data from a carcinoma of left lower outer quadrant patient

Genome and transcriptome sequence data from a ductal carcinoma of left breast patient

Genome and transcriptome sequence data from an infiltrating ductal carcinoma of right breast patient

Genome and transcriptome sequence data from an adenocarcinoma of lung patient

Genome and transcriptome sequence data from a metastatic neuroendocrine carcinoma patient

Genome and transcriptome sequence data from an adnexal tumor probable of Wolffian origin patient

Genome and transcriptome sequence data from an adenomacarcinoma of vulva patient

Genome and transcriptome sequence data from a neuroendocrine tumor likely pancreatic origin patient

Genome and transcriptome sequence data from a metastatic adenocarcinoma of the GE junction patient

Genome and transcriptome sequence data from a pancreatic ductal adenocarcinoma patient

Genome and transcriptome sequence data from a medullary thyroid carcinoma patient

Genome and transcriptome sequence data from an invasive ductal carcinoma of left breast patient

Genome and transcriptome sequence data from a metastatic breast carcinoma patient

Genome and transcriptome sequence data from a clear cell carcinoma of ovary patient

Genome and transcriptome sequence data from a pleomorphic spindle cell sarcoma patient

Genome and transcriptome sequence data from an invasive carcinoma of left breast patient

Genome and transcriptome sequence data from a metastatic gastric adenocarcinoma patient

Genome and transcriptome sequence data from a squamous cell carcinoma of anus patient

Genome and transcriptome sequence data from an adenoid cystic carcinoma of the trachea patient