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A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies
Published on: July 28, 2020
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Integrated case-control and somatic-germline interaction analyses of soft-tissue sarcoma.
Fulan Hu1,2, Yao Yu2, Jiun-Sheng Chen2
1Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, China.
Journal of Medical Genetics
|May 25, 2020
Summary
Rare genetic variations in NF1, RB1, TP53, and MSH2 are linked to soft-tissue sarcoma (STS) risk. BAG1 is identified as a novel gene associated with STS development.
Area of Science:
- Genetics
- Oncology
- Cancer Genomics
Background:
- Rare genetic variations contribute to cancer development, but their role in soft-tissue sarcoma (STS) is not well understood.
- Identifying genes associated with STS susceptibility is crucial for understanding its etiology and developing targeted therapies.
Purpose of the Study:
- To investigate the contribution of rare genetic variation to the development of soft-tissue sarcoma (STS).
- To identify and characterize genes predisposing individuals to STS through a case-control and somatic-germline interaction study.
Main Methods:
- Whole-exome sequencing was performed on 219 STS cases from The Cancer Genome Atlas and 3507 genetically matched controls of European ancestry.
- Gene-based association tests were conducted using VAAST 2, with cross-platform technological stratification performed using XPAT.
Main Results:
- The gene NF1 showed the strongest genome-wide association signal (p=1×10⁻⁵) across STS subtypes.
- Significant associations were also observed for TP53, RB1, MSH2, and the novel candidate gene BAG1.
- Truncating variants in NF1 and MSH2, and damaging missense variants in RB1 and BAG1, were primarily responsible for the observed association signals.
Conclusions:
- Pathogenic variants in NF1, RB1, and TP53 significantly increase the risk for multiple STS subtypes.
- MSH2 is implicated in STS susceptibility, and BAG1 is identified as a novel risk gene for STS.
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