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Updated: Jul 11, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Copy number variants landscape of multiple cancers and clinical applications based on NGS gene panel
Kangpeng Yan1, Li Niu2, Boyu Wu3
1Department of Abdominal Oncology Surgery, Jiangxi Cancer Hospital, Nanchang, China.
Background:
The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood.
Methods:
We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs.
Results:
We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (p = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs.
Conclusion:
The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.
Insights
This study identified 16 common and 22 cancer-specific copy number variants (CNVs) across 15 cancer types. These CNVs can guide pan-cancer drug design and serve as unique diagnostic markers for various cancers.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Next-generation sequencing (NGS) in oncology detects shared molecular biomarkers across tumor types.
- Intra-tumor heterogeneity poses a challenge for therapeutic resistance.
- Tumor-related copy number variants (CNVs) are key regulators in cancer but poorly understood across diverse cancers.
Purpose of the Study:
- To conduct a pan-cancer analysis of CNVs in cancer-related genes.
- To identify common and cancer-specific CNVs.
- To explore the utility of CNVs in cancer classification and targeted therapy.
Main Methods:
- Pan-cancer CNV analysis of 15 cancer types (1438 patients) using NGS and a commercial panel.
- Bioinformatics analysis for CNV detection, clustering, and frequency comparison.
- LASSO analysis for identifying critical CNVs.
Main Results:
- Identified 523 CNVs, including 16 common and 22 cancer-specific variants.
- FAM58A was frequently detected, with significant differences between sexes (p=0.001).
- Common CNVs like FOXA1 and NFKBIA, involved in gene transcription, were frequently mutated. 11 key features, including sex and specific genes, were identified for cancer classification.
Conclusions:
- The 16 common CNVs can inform pan-cancer drug design and targeted therapies.
- The 22 cancer-specific CNVs offer potential as unique diagnostic markers for individual cancer types.
