Project description:In this study, we investigated somatic mutations of CD4+ and CD8+ T cells in patients with immune-mediated aplastic anemia (AA). To understand the role of mutations, we performed single-cell level analysis of 6 longitudinal samples of 2 AA patients carrying STAT3 or KRAS and other mutations in CD8+ T cells. The analysis was performed using V(D)J and 5' gene expression platform (10X Genomics). STAT3 mutated clone was clearly distinguishable from other CD8+ T cells and showed a cytotoxic phenotype, attenuated by successful immunosuppressive treatment. Our results suggest that somatic mutations in T cells can alter T cell phenotype warranting further investigation of their role in the pathogenesis of immune-mediated AA.
Project description:Natural killer/T-cell lymphoma (NKTCL) is a malignant proliferation of CD56+/cytoCD3+ lymphocytes and constitutes a heterogeneous group of aggressive lymphomas prevalent in Asian and South American populations. Molecular pathogenesis of NKTCL remains largely elusive. Here we identified somatic mutations in RNA helicase gene DDX3X. Gene expression profiling revealed an association of DDX3X mutations with activation of NF-kB and MAPK pathways. Together, our work suggests the heterogeneity of gene mutational spectrum in NKTCL.
Project description:Tumor Infiltrating Lymphocytes (TIL) recognize unique somatic mutations and mediate objective clinical responses in metastatic breast cancer
Project description:Tumor Infiltrating Lymphocytes (TIL) recognize unique somatic mutations and mediate objective clinical responses in metastatic breast cancer