Microsatellite instability: A 2024 update

作者：Hiroyuki Yamamoto, Yoshiyuki Watanabe, Hiroyuki Arai, Kumiko Umemoto, Keisuke Tateishi, Yu Sunakawa · 发表于：Cancer Science · 年份：2024 · DOI：10.1111/cas.16160 · 被引用次数：63 · 研究领域：Space exploration and regulation、Space Satellite Systems and Control、Spacecraft Design and Technology

Deficient mismatch repair (dMMR) results in microsatellite instability (MSI), a pronounced mutator phenotype. High-frequency MSI (MSI-H)/dMMR is gaining increasing interest as a biomarker for advanced cancer patients to determine their eligibility for immune checkpoint inhibitors (ICIs). Various methods based on next-generation sequencing (NGS) have been developed to assess the MSI status. Comprehensive genomic profiling (CGP) testing can precisely ascertain the MSI status as well as genomic alterations in a single NGS test. The MSI status can be also ascertained through the liquid biopsy-based CGP assays. MSI-H has thus been identified in various classes of tumors, resulting in a greater adoption of immunotherapy, which is hypothesized to be effective against malignancies that possess a substantial number of mutations and/or neoantigens. NGS-based studies have also characterized MSI-driven carcinogenesis, including significant rates of fusion kinases in colorectal cancers (CRCs) with MSI-H that are targets for therapeutic kinase inhibitors, particularly in MLH1-methylated CRCs with wild-type KRAS/BRAF. NTRK fusion is linked to the colorectal serrated neoplasia pathway. Recent advances in investigations of MSI-H malignancies have resulted in the development of novel diagnostic or therapeutic techniques, such as a synthetic lethal therapy that targets the Werner gene. DNA sensing in cancer cells is required for antitumor immunity induced by dMMR, opening up novel avenues and b...