Diffuse Intrinsic Pontine Glioma (DIPG) is a highly morbid form of pediatric brainstem glioma. Here, we present the first comprehensive protein, mRNA, and methylation profiles of fresh frozen DIPG specimens (n=14), normal brain tissue (n=10), and other pediatric brain tumors (n=17). Protein profiling identified 2,305 unique proteins indicating distinct DIPG protein expression patterns compared to other pediatric brain tumors. Western blot and immunohistochemistry validated upregulation of Clusterin (CLU), Elongation Factor 2 (EF2), and Talin-1 (TLN1) in DIPGs studied. Comparisons to mRNA expression profiles generated from tumor and adjacent normal brain tissue indicated two DIPG subgroups, characterized by upregulation of Myc (N-Myc) or Hedgehog (Hh) signaling. We validated upregulation of PTCH, a membrane receptor in the Hh signaling pathway, in a subgroup of DIPG specimens. DNA methylation analysis indicated global hypomethylation of DIPG compared to adjacent normal tissue specimens, with differential methylation of 24 genes involved in Hh and Myc pathways, correlating with protein and mRNA expression patterns. Sequencing analysis showed c.83A>T mutations in the H3F3A or HIST1H3B gene in 77% of our DIPG cohort. Supervised analysis revealed a unique methylation pattern in mutated specimens compared to the wild type DIPG samples.
This study presents the first comprehensive multidimensional protein, mRNA, and methylation profiling of pediatric brain tumor specimens, detecting the presence of two subgroups within our DIPG cohort. This multidimensional analysis of DIPG provides increased analytical power to more fully explore molecular signatures of DIPGs, with implications for evaluating potential molecular subtypes and biomarker discovery for assessing response to therapy.
We conclude that TLIF is a safe and effective method of achieving lumbar fusion with a 93% radiographic fusion success and a nearly 80% rate of overall patient satisfaction but frequently results in incomplete relief of symptoms. Complications resulting from the procedure are uncommon and generally minor and transient.
Fibrin-associated diffuse large B cell lymphoma (FA-DLBCL) is a rare Epstein-Barr viruspositive B cell lymphoma that is nonmassforming, does not directly produce symptoms, and is incidentally discovered on histological examination of tissues excised for other reasons. Despite overlap in morphologic and immunophenotypic features with aggressive B cell neoplasms, FA-DLBCL shows an excellent clinical outcome, even with surgical excision alone. We report an extremely rare occurrence of FA-DLBCL found in association with a metallic implant on revision arthroplasty of the knee. This report also illustrates the need for an integrated multidisciplinary approach for accurate diagnosis and avoidance of overtreatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.