Department of Hematology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, 361102, China.
National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, 361102, China.
BMC Med Genomics. 2021 May 31;14(1):142. doi: 10.1186/s12920-021-00984-1.
Allelic imbalance (AI) in tumors is caused by chromosomal and sub-chromosomal gains and losses.
We evaluated AI at 109,086 germline exonic SNP loci in four cancer types, and identified a set of SNPs that demonstrate strong tumor allele specificity in AI events. Further analyses demonstrated that these alleles show consistently different frequencies in the cancer population compared to the healthy population and are significantly enriched for predicted protein-damaging variants. Moreover, genes harboring SNPs that demonstrate allele specificity are enriched for cancer-related biological processes and are more likely to be essential in cancer cells.
In summary, our study provides a unique and complementary method to identify genes and variants that are relevant to carcinogenesis.
肿瘤中的等位基因失衡(AI)是由染色体和亚染色体的增益和缺失引起的。
我们在四种癌症类型的 109086 个种系外显子 SNP 位点评估了 AI,并鉴定出了一组在 AI 事件中表现出强烈肿瘤等位基因特异性的 SNP。进一步的分析表明,与健康人群相比,这些等位基因在癌症人群中的频率始终不同,并且显著富集了预测的蛋白损伤变体。此外,携带表现出等位基因特异性的 SNP 的基因富集了与癌症相关的生物学过程,并且在癌细胞中更可能是必需的。
总之,我们的研究提供了一种独特而互补的方法来鉴定与致癌作用相关的基因和变体。