See the published version of this article at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Distinct Mutation Profiles Between Primary Bladder Cancer and Circulating Tumor Cells Warrant the Use of Circulating Tumors Cells as Cellular Resource for Mutation Follow-up
U-Syn Ha
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Cancer.
Background
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. Genome sequencing of bladder tumor and circulating tumor cells is highlighted to identify the somatic mutations of primary bladder cancer.
Methods
Bladder 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.
Results
We 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.
Conclusions
The 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 registration:
Patients were selected and registered retrospectively, and medical records were evaluated.
Keywords
Bladder cancer, Circulating Tumor Cells, Mutation
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
No comments provided
Editorial decision: Minor revision
On 18 Nov, 2020
Editor assigned
On 03 Nov, 2020
Editor invited
On 03 Nov, 2020
Submission checks complete
On 30 Oct, 2020
Version 1
Posted 10 Jul, 2020
No comments provided
Editorial decision: Major revision
On 26 Oct, 2020
Review #2 received
Received 22 Oct, 2020
Reviewer #2 agreed
On 19 Oct, 2020
Review #1 received
Received 15 Oct, 2020
Reviewer #1 agreed
On 23 Sep, 2020
Reviewers invited
Invitations sent on 21 Aug, 2020
Submission checks complete
On 09 Jul, 2020
Editor invited
On 09 Jul, 2020
Editor assigned
On 09 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at BMC Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Distinct Mutation Profiles Between Primary Bladder Cancer and Circulating Tumor Cells Warrant the Use of Circulating Tumors Cells as Cellular Resource for Mutation Follow-up
U-Syn Ha
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
No comments provided
Editorial decision: Minor revision
On 18 Nov, 2020
Editor assigned
On 03 Nov, 2020
Editor invited
On 03 Nov, 2020
Submission checks complete
On 30 Oct, 2020
Version 1
Posted 10 Jul, 2020
No comments provided
Editorial decision: Major revision
On 26 Oct, 2020
Review #2 received
Received 22 Oct, 2020
Reviewer #2 agreed
On 19 Oct, 2020
Review #1 received
Received 15 Oct, 2020
Reviewer #1 agreed
On 23 Sep, 2020
Reviewers invited
Invitations sent on 21 Aug, 2020
Submission checks complete
On 09 Jul, 2020
Editor invited
On 09 Jul, 2020
Editor assigned
On 09 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Cancer.
Background
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. Genome sequencing of bladder tumor and circulating tumor cells is highlighted to identify the somatic mutations of primary bladder cancer.
Methods
Bladder 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.
Results
We 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.
Conclusions
The 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 registration:
Patients were selected and registered retrospectively, and medical records were evaluated.
Figure 1
Figure 2
Figure 3