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Research article
Tao Luo
Third Military Medical University Southwest Hospital Department of Pathology
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Aims
Tumor mutational burden (TMB) is a biomarker for immune checkpoint therapy. The impact of TMB on clinical outcomes and the correlation coefficient between exome sequencing and targeted sequencing in glioma have not yet been explored.
Methods
Somatic mutations in the coding regions of 897 primary gliomas, clinical and RNA-seq information for 654 patients In TCGA dataset were analyzed. Descriptive and correlational analyses were conducted with TMB. Enrichment Map and GSEA was also performed.
Results
TMB was higher for the group of mutant genes that are frequently mutated in glioblastomas (GBMs) and lower for the group of mutant genes that are frequently mutated in lower-grade gliomas (LGGs). Patients with a higher TMB exhibited shorter overall survival. TMB was associated with grade, age, subtype and mutations affecting genomic structure. The signaling pathways of the cell cycle and immune effector processes were enriched in the TMBHigh group. TMB was higher in the mismatch repair (MMR) gene mutant group compared to the wildtype group, but the MMR pathway was enriched in the TMBHigh group of gliomas without mutations in classical MMR genes. The correlation between TMBs calculated through exome sequencing and targeted sequencing was moderate.
Conclusions
TMB is associated with poor outcomes in diffuse glioma. High proliferative activity in the TMBHigh group could account for the shorter survival of these patients. This association was not reflected by a pan-cancer targeted sequencing panel.
Keywords
TMB, glioma, prognosis, Pan-cancer targeted sequencing
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CURRENT STATUS: Published
View the published article at BMC Cancer.
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Editor assigned
On 10 Feb, 2020
Submission checks complete
On 09 Feb, 2020
Editor invited
On 09 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 29 Jan, 2020
Review #1 received
Received 15 Jan, 2020
Reviewer #2 agreed
On 12 Jan, 2020
Reviewers invited
Invitations sent on 03 Jan, 2020
Reviewer #1 agreed
On 03 Jan, 2020
Editor assigned
On 27 Dec, 2019
Submission checks complete
On 26 Dec, 2019
Editor invited
On 26 Dec, 2019
No comments provided
Editorial decision: Major revision
On 02 Dec, 2019
Review #2 received
Received 24 Nov, 2019
Review #1 received
Received 05 Nov, 2019
Reviewer #2 agreed
On 31 Oct, 2019
Reviewers invited
Invitations sent on 29 Oct, 2019
Reviewer #1 agreed
On 29 Oct, 2019
Editor assigned
On 28 Oct, 2019
Submission checks complete
On 27 Oct, 2019
Editor invited
On 27 Oct, 2019
Version 1
Posted 24 Jul, 2019
No comments provided
Editorial decision: Major revision
On 23 Sep, 2019
Review #2 received
Received 20 Sep, 2019
Reviewer #2 agreed
On 13 Sep, 2019
Review #1 received
Received 12 Sep, 2019
Reviewers invited
Invitations sent on 28 Aug, 2019
Reviewer #1 agreed
On 28 Aug, 2019
Submission checks complete
On 19 Jul, 2019
Editor assigned
On 19 Jul, 2019
Editor invited
On 18 Jul, 2019
First submitted
On 15 Jul, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint 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
Tao Luo
Third Military Medical University Southwest Hospital Department of Pathology
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
View the published article at BMC Cancer.
No community comments so far
Editor assigned
On 10 Feb, 2020
Submission checks complete
On 09 Feb, 2020
Editor invited
On 09 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 29 Jan, 2020
Review #1 received
Received 15 Jan, 2020
Reviewer #2 agreed
On 12 Jan, 2020
Reviewers invited
Invitations sent on 03 Jan, 2020
Reviewer #1 agreed
On 03 Jan, 2020
Editor assigned
On 27 Dec, 2019
Submission checks complete
On 26 Dec, 2019
Editor invited
On 26 Dec, 2019
No comments provided
Editorial decision: Major revision
On 02 Dec, 2019
Review #2 received
Received 24 Nov, 2019
Review #1 received
Received 05 Nov, 2019
Reviewer #2 agreed
On 31 Oct, 2019
Reviewers invited
Invitations sent on 29 Oct, 2019
Reviewer #1 agreed
On 29 Oct, 2019
Editor assigned
On 28 Oct, 2019
Submission checks complete
On 27 Oct, 2019
Editor invited
On 27 Oct, 2019
Version 1
Posted 24 Jul, 2019
No comments provided
Editorial decision: Major revision
On 23 Sep, 2019
Review #2 received
Received 20 Sep, 2019
Reviewer #2 agreed
On 13 Sep, 2019
Review #1 received
Received 12 Sep, 2019
Reviewers invited
Invitations sent on 28 Aug, 2019
Reviewer #1 agreed
On 28 Aug, 2019
Submission checks complete
On 19 Jul, 2019
Editor assigned
On 19 Jul, 2019
Editor invited
On 18 Jul, 2019
First submitted
On 15 Jul, 2019
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 article at BMC Cancer.
Aims
Tumor mutational burden (TMB) is a biomarker for immune checkpoint therapy. The impact of TMB on clinical outcomes and the correlation coefficient between exome sequencing and targeted sequencing in glioma have not yet been explored.
Methods
Somatic mutations in the coding regions of 897 primary gliomas, clinical and RNA-seq information for 654 patients In TCGA dataset were analyzed. Descriptive and correlational analyses were conducted with TMB. Enrichment Map and GSEA was also performed.
Results
TMB was higher for the group of mutant genes that are frequently mutated in glioblastomas (GBMs) and lower for the group of mutant genes that are frequently mutated in lower-grade gliomas (LGGs). Patients with a higher TMB exhibited shorter overall survival. TMB was associated with grade, age, subtype and mutations affecting genomic structure. The signaling pathways of the cell cycle and immune effector processes were enriched in the TMBHigh group. TMB was higher in the mismatch repair (MMR) gene mutant group compared to the wildtype group, but the MMR pathway was enriched in the TMBHigh group of gliomas without mutations in classical MMR genes. The correlation between TMBs calculated through exome sequencing and targeted sequencing was moderate.
Conclusions
TMB is associated with poor outcomes in diffuse glioma. High proliferative activity in the TMBHigh group could account for the shorter survival of these patients. This association was not reflected by a pan-cancer targeted sequencing panel.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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