| 项目编号 |
PRJCA037859 |
| 项目标题 |
Application of germline-somatic association analysis in colorectal cancer and development of novel mutational signature analysis algorithm for targeted sequencing data |
| 涉及领域 |
Medical |
| 数据类型 |
Raw sequence reads
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| 物种名称 |
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| 描述信息 |
Background: Among colorectal cancer (CRC) patients, it was reported that clinical guideline-directed genetic testing would omit 33%-61% of pathogenic or likely pathogenic (P/LP) germline mutations (GMs) compared to research-based universal sequencing. Most of these omitted GMs were located in non-mismatch repair (non-MMR) genes, such as BRCA1/2, RecQ helicase genes, and ATM. It remains largely unclear whether and how these non-MMR genes are associated with CRC tumorigenesis. A somatic single base substitution (SBS) signature is defined as a specific combination of 96 different mutation types, each characterized by the SBS and its flanking nucleotides. SBS signatures can provide insights into the mutagenic processes that shape a cancer genome. However, there are methodological issues regarding the application of SBS signature analysis to targeted sequencing data, where the SBS count per patient is typically low. Objective: This project aims to identify CRC-predisposing GMs among common cancer susceptibility genes and investigate their potential influences on CRC somatic mutational features. We secondarily aim to develop a novel mutational signature analysis algorithm tailored for targeted sequencing data. This algorithm will be used to extract somatic SBS features and embedded in a comprehensive germline-somatic association analysis for CRC. Methods: This project plans to retrospectively analyze the paired tumor-normal sequencing data from a total of 3,240 Chinese CRC patients. Targeted next-generation sequencing (NGS) was performed using the GenePlus 1021-gene panel. Main analyses of this project will be conducted among 2,405 patients, and key findings will be subjected to validation in the remaining 835 patients. Monte Carlo simulations and real-data applications will be conducted to test the newly proposed method. |
| 样品范围 |
Multiisolate |
| 发布日期 |
2025-03-26 |
| 数据提供者 |
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| 实验材料提供者 |
Geneplus-Beijing Institute |
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| No funding support
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| 提交者 |
Jinzhu
Jia (jzjia@math.pku.edu.cn)
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| 提交单位 |
Peking University Health Science Center |
| 提交日期 |
2025-03-26 |
