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A multi-ethnic germline-somatic association database deciphers multilayered and interconnected genetic mutations in cancer.

Junyi XinZongchao MoRui-Chao ChaiWei HuaJi-Guang Wang
Published in: Cancer research (2023)
Inherited germline and acquired somatic alterations can both promote human tumor development. Elucidating the cooperation between somatic and germline genetic alterations that drive tumorigenesis could help inform precision cancer prevention and treatment strategies. Here, leveraging genomic genotyping and sequencing data from 9,029 cancer patients with European, East Asian, and African ancestry, we performed a pan-cancer analysis to evaluate the associations between germline single nucleotide polymorphisms (SNPs) and somatic alterations, including single-nucleotide variant and small insertion/deletion mutations, copy number variation (CNV), tumor mutational burden (TMB), and mutational signatures. Genome-wide significant germline-somatic pairs were abundant, and most of the associations were observed in one cancer type and one ancestry group. A user-friendly interactive Multi-ethnic Germline-Somatic Association (MGSA) database (http://wanglab-hkust.cn:3838/MGSA/) was developed, which can be used to query, browse, and download the results of the association analyses. Moreover, the MGSA database offers additional survival analysis and functional annotation. Together, this work provides a resource for uncovering the clinical and biological roles of associations between germline variants and somatic alterations in human cancer.
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