Tubacher Emmanuel, How-Kit Alexandre, Sahbatou Mourad, Duval Alex, Renault Victor, Deleuze Jean-François
Laboratory for bioinformatics, Fondation Jean DAUSSET Centre d'Etude du Polymorphisme Humain, Paris, France.
Laboratory for Genomics, Fondation Jean Dausset Centre d'Etude du Polymorphisme Humain, Paris, France.
Front Genet. 2025 Apr 24;16:1523278. doi: 10.3389/fgene.2025.1523278. eCollection 2025.
Microsatellite instability (MSI) is becoming increasingly important in oncology as it has been reported across more than two dozen of solid cancer types. The MSI-high phenotype has long been used as a predictive and prognostic marker in colorectal cancer and has been recently approved by the FDA as a marker for immune checkpoint blockade therapy for solid cancers. Several bioinformatics tools have been developed to assess MSI status of a tumor sample using Next-Generation Sequencing (NGS) data mostly from whole genome, whole exome, and targeted gene sequencing data. While most tools available only infer the MSI status, none of them use RNA-sequencing (RNA-seq) data and provide per microsatellite expression and genotype results. We present MSI Expresso, a software which assesses the MSI status by testing the instability of a panel of 3'UTR microsatellites from RNA-seq data and also provides a detailed landscape of MSI-related events such as exon skipping, unstable coding and intronic microsatellites with a graphical output of the recurrent events. MSI Expresso's ability to detect the MSI status was assessed from RNA-seq data of 228 colon, 13 prostate and two endometrial cancer samples with known MSI status and achieved almost 100% concordant results. Thus, MSI Expresso is a new tool for MSI detection from RNA-sequencing data complementary to genomic and genetic approaches allowing to explore the consequence of MSI events on transcripts/transcriptome.
微卫星不稳定性（MSI）在肿瘤学中变得越来越重要，因为据报道它存在于二十多种实体癌类型中。MSI高表型长期以来一直被用作结直肠癌的预测和预后标志物，最近已被美国食品药品监督管理局（FDA）批准作为实体癌免疫检查点阻断疗法的标志物。已经开发了几种生物信息学工具，主要使用来自全基因组、全外显子组和靶向基因测序数据的下一代测序（NGS）数据来评估肿瘤样本的MSI状态。虽然大多数现有工具仅推断MSI状态，但它们都不使用RNA测序（RNA-seq）数据，也不提供每个微卫星的表达和基因型结果。我们展示了MSI Expresso，这是一款软件，它通过测试来自RNA-seq数据的一组3'UTR微卫星的不稳定性来评估MSI状态，还提供MSI相关事件的详细情况，如外显子跳跃、不稳定编码和内含子微卫星，并以循环事件的图形输出呈现。从228个已知MSI状态的结肠癌、13个前列腺癌和2个子宫内膜癌样本的RNA-seq数据中评估了MSI Expresso检测MSI状态的能力，结果显示几乎100%一致。因此，MSI Expresso是一种从RNA测序数据中检测MSI的新工具，它是对基因组和遗传方法的补充，能够探索MSI事件对转录本/转录组的影响。
