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.
Research
Whole-Exome Sequencing Identifies Somatic Mutations Associated With Lung Cancer Metastasis to the Brain
Pengcheng Li
Department of Thoracic Oncology, Wuhan Union hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Lung cancer is the most aggressive cancer which representing one-quarter of all cancer-related deaths, and metastatic spread accounts for >70% of these deaths, especially brain metastasis. Metastasis associated mutations are important biomarkers for metastasis prediction and outcome improvement.
Methods: In this study, we applied whole-exome sequencing to identify potential metastasis related mutation in 12 paired lung cancer and brain metastasis samples.
Results: We identified 1,702 SNVs and 6,131 mutation events in 1,220 genes. Furthermore, we identified several lung cancer metastases associated genes (KMT2C, AHNAK2). A mean of 3.1 driver gene mutation events per tumor with the dN/dS of 2.13 indicating a significant enrichment for cancer driver gene mutations. Mutation spectrum analysis found lung-brain metastasis samples have more similar Ti/Tv(transition/transversion) profile with brain cancer in which C>T transitions are more frequently while lung cancer has more C>A transversion. We also found the most important tumor onset and metastasis pathways such as chronic myeloid leukemia, ErbB signaling pathway and glioma pathway. Finally, we identified a significant survival associated mutation gene ERF in both TCGA (P=0.01) and our dataset (P=0.012). Conclusion: In summary, we conducted a pairwise lung-brain metastasis based exome-wide sequencing and identified some novel metastasis related mutations which provided potential biomarkers for prognosis and targeted therapeutics.
Keywords
whole-exome sequencing, lung cancer, somatic mutation, brain metastasis
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
- supplementarytable1.xlsx
Table S1. Clinicopathological information of the 12 NSCLC patients. LC, Lung cancer; BM, brain metastasis;
- Supplementarytable2.xlsx
Table S2. Enriched pathway of frequently mutated genes.
- Supplementarytable3.xlsx
Table S3. Keywords Enriched analysis of frequently mutated genes.
- supplementaryfigure1.tif
Figure S1 (A) Number of variants, (B) classification of variant, (C) TMB of each patient and (D) the correlation between TMB of LC and BM
- supplementaryfigure2.tif
Figure S2 Copy number variations in lung tumor and brain tumor samples.
- supplementaryfigure3.tif
Figure S3 Survival analysis between mutations in LC and overall survival times
- supplementaryfigure4.tif
Figure S4 Survival analysis between mutations in BM and overall survival times
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 21 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Translational Medicine
Learn more about our company.
This is a preprint. It has not completed peer review.
Research
Whole-Exome Sequencing Identifies Somatic Mutations Associated With Lung Cancer Metastasis to the Brain
Pengcheng Li
Department of Thoracic Oncology, Wuhan Union hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 21 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Translational Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Lung cancer is the most aggressive cancer which representing one-quarter of all cancer-related deaths, and metastatic spread accounts for >70% of these deaths, especially brain metastasis. Metastasis associated mutations are important biomarkers for metastasis prediction and outcome improvement.
Methods: In this study, we applied whole-exome sequencing to identify potential metastasis related mutation in 12 paired lung cancer and brain metastasis samples.
Results: We identified 1,702 SNVs and 6,131 mutation events in 1,220 genes. Furthermore, we identified several lung cancer metastases associated genes (KMT2C, AHNAK2). A mean of 3.1 driver gene mutation events per tumor with the dN/dS of 2.13 indicating a significant enrichment for cancer driver gene mutations. Mutation spectrum analysis found lung-brain metastasis samples have more similar Ti/Tv(transition/transversion) profile with brain cancer in which C>T transitions are more frequently while lung cancer has more C>A transversion. We also found the most important tumor onset and metastasis pathways such as chronic myeloid leukemia, ErbB signaling pathway and glioma pathway. Finally, we identified a significant survival associated mutation gene ERF in both TCGA (P=0.01) and our dataset (P=0.012). Conclusion: In summary, we conducted a pairwise lung-brain metastasis based exome-wide sequencing and identified some novel metastasis related mutations which provided potential biomarkers for prognosis and targeted therapeutics.
Figure 1
Figure 2
Figure 3
Figure 4