Mouse Anti-Human CD45RO monoclonal antibody, clone JID648

T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated. We identified recurrently mutated genes previously unknown to be mutated in T-PLL, which are SAMHD1, HERC1, HERC2, PRDM2, PARP10, PTPRC, and FOXP1. SAMHD1 regulates cellular deoxynucleotide levels and acts as a potential tumor suppressor in other leukemias. We observed destructive mutations in 18% of cases as well as deletions in two further cases. Taken together, we identified additional genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, and HERC2) as being recurrently mutated in T-PLL. Thus, our study considerably extends the picture of pathways involved in molecular pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with similar to 20% of T-PLL affected by destructive lesions likely as major player in T-PLL pathogenesis.

Introduction: Inflammatory breast cancer (IBC) is a rare type of breast cancer with poor prognosis, and the pathogenesis of this life-threatening disease is yet to be fully elucidated. This study aims to identify key genes of IBC, which could be potential diagnostic or therapeutic targets. Methods: Four datasets GSE5847, GSE22597, GSE23720, and GSE45581 were downloaded from the Gene Expression Omnibus (GEO) and differential expression analysis was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to understand the potential bio-functions of the differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was constructed for functional modules analysis and hub genes identification, and TCGA survival analysis and qRT-PCR of clinical samples were used to further explore and validate the effect of hub genes on IBC. Results: A total of 114 DEGs were identified from the GEO datasets. GO and KEGG analyses showed that the DEGs were mainly enriched in oncogenesis and cell adhesion. From the PPI network, we screened out five hub genes, including PTPRC, IL6, SELL, CD40, and SPN. Survival analysis and expression validation verified the robustness of the hub genes. Discussion: The present study provides new insight into the understanding of IBC pathogenesis and the identified hub genes may serve as potential targets for diagnosis and treatment.