Abstract
BackgroundWhile circulating tumor cells may serve as minimally invasive cancer markers for bladder cancers, the relationship between primary bladder cancers and circulating tumor cells in terms of somatic mutations is largely unknown. Genome sequencing of bladder tumor and circulating tumor cells is highlighted to identify the somatic mutations of primary bladder cancer.MethodsBladder cancer tissue was collected by transurethral resection of the bladder and preserved by snap-freezing. Circulating tumor cells were Isolated from the blood obtained before treatment. We performed whole exome sequencing of 20 matched pairs of primary bladder cancers and circulating tumor cells to identify and compare somatic mutations of these two different genomic resources.ResultsWe observed that mutation abundances of primary bladder cancers and circulating tumor cells were highly variable. The mutation abundance was not significantly correlated between matched pairs. Of note, the mutation concordance between two resources was only 3–24% across 20 pairs examined, suggesting that the circulating tumor cell genomes of bladder cancer patients might be genetically distinct from primary bladder cancers. A relative enrichment of mutations belonging to APOBEC-related signature and a depletion of C-to-G transversions were observed for primary- and circulating tumor cells specific mutations, respectively, suggesting that distinct mutation forces might have been operative in respective lesions during carcinogenesis.ConclusionsThe observed discrepancy of mutation abundance and low concordance level of mutations between genomes of primary bladder cancers and circulating tumor cells should be taken into account when evaluating clinical utility of circulating tumor cells for treatments and follow-up of bladder cancers.Trial registrationPatients were selected and registered retrospectively, and medical records were evaluated.
Highlights
While circulating tumor cells may serve as minimally invasive cancer markers for bladder cancers, the relationship between primary bladder cancers and circulating tumor cells in terms of somatic mutations is largely unknown
Primary short-term culture of CTCs CTCs retrieved on the high-density microporous (HDM) chip were washed with phosphate buffered saline (PBS) and cultured in 6-well Costar® Ultra-Low Attachment plates (Costar®; Corning Korea Company, Ltd., Fig. 1 Representative immunostaining images showing circulating tumor cells (CTCs) with 4′,6-diamidino-2-phenylindole (DAPI), Vimentin, Cytokeratin, and CD45 positive
Patients A total of 20 patients with non-metastatic bladder cancer were enrolled in this study
Summary
While circulating tumor cells may serve as minimally invasive cancer markers for bladder cancers, the relationship between primary bladder cancers and circulating tumor cells in terms of somatic mutations is largely unknown. Bladder cancer is a widespread and highly heterogeneous malignancy. Clinical outcome of this disease is poor because of its highly recurrent nature with frequent disease progression and treatment failure [1]. Patients with advanced bladder cancer are at high risk of disease recurrence or progression, with half of them having relapse after radical surgery. 30–80% of bladder cancer patients with advanced disease below pT1 stages experienced disease recurrence and up to 45% of cases progressed to muscle invasion within 5 years [2,3,4]. Bladder cancer is characterized with variable clinical outcomes requiring frequent follow-up and repeated treatments, making this disease obstinate and challengeable to overcome
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