林奇综合征
微卫星不稳定性
移码突变
MSH2
DNA错配修复
MSH6型
背景(考古学)
MLH1
生物信息学
生物
癌症
计算生物学
索引
遗传学
癌症研究
突变
基因
微卫星
结直肠癌
古生物学
等位基因
基因型
单核苷酸多态性
作者
Ana María Bolívar,Fahriye Duzagac,Krishna M. Sinha,Eduardo Vilar
标识
DOI:10.1016/j.mam.2023.101204
摘要
Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6 and PMS2. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are the most common. As a result, MMR-deficient (MMRd) cells generate increased rates of tumor-specific neoantigens (neoAgs) that can be recognized by the immune system to activate cancer cell killing. In this context, LS is an ideal disease to leverage immune-interception strategies. Therefore, the identification of these neoAgs is an ongoing effort for the development of LS cancer preventive vaccines. In this review, we summarize the computational methods used for in silico neoAg prediction, including their challenges, and the experimental techniques used for in vitro validation of their immunogenicity. In addition, we outline results from past and on-going vaccine clinical trials and highlight avenues for improvement and future directions.
科研通智能强力驱动
Strongly Powered by AbleSci AI