Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)–mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation. As tumor grade increases, we find enhanced proliferation of malignant cells, larger pools of undifferentiated glioma cells, and an increase in macrophage over microglia expression programs in TME. Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissecting the differences among human tumor subclasses.
Authors: Andrew S. Venteicher, Itay Tirosh, Christine Hebert, Keren Yizhak, Cyril Neftel, Mariella G. Filbin, Volker Hovestadt, Leah E. Escalante, McKenzie L. Shaw, Christopher Rodman, Shawn M. Gillespie, Danielle Dionne, Christina C. Luo, Hiranmayi Ravichandran, Ravindra Mylvaganam, Christopher Mount, Maristela L. Onozato, Brian V. Nahed, Hiroaki Wakimoto, William T. Curry, A. John Iafrate, Miguel N. Rivera, Matthew P. Frosch, Todd R. Golub, Priscilla K. Brastianos, Gad Getz, Anoop P. Patel, Michelle Monje, Daniel P. …
Conditions: Glioma; BRAF V600E; Pleomorphic Xantho-Astrocytoma; Glioblastoma Intervention: Procedure: Surgical Cohort Sponsors: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Musella Foundation Recruiting
Conclusion: GKR could be an additional treatment option in recurrent high-grade glioma, particularly in patients with good PS and limited tumor volume.
PMID: 29991111 [PubMed]
The next in our ” Best of the Month ” series comes fromMay, 30, 2018:Despite the fact that the most recent update of the World Health Organization (WHO) classification of central nervous system tumors was published only two years ago, the data is already showing that we are moving beyond that classification system when if comes to IDH-wildtype diffuse astrocytomas. The concept of an ” integrated diagnosis ” in the setting of IDH-wildtype histologic grade II and III tumors has already been eclipsed in the literature by the primacy of the genetic signature over histologic appearance in predicting outcome….
Authors: Martynov BV, Kholyavin AI, Nizkovolos VB, Parfenov VE, Trufanov GE, Svistov DV
Surgical resection of gliomas affecting functionally important brain structures is associated with high risk of permanent postoperative neurological deficit and deterioration of the patient’s quality of life. The availability of modern neuroimaging and neuronavigation permits the application of minimally invasive stereotactic cryodestruction of the tumor in such cases. The authors used this treatment in 88 patients with supratentorial gliomas of various WHO histopathological grades not suitable for microsurgical resecti…
Brain tumors are the most common malignancy of childhood. Approximately 50% of pediatric CNS tumors are astrocytomas, most low grade. Low grade glioma (LGG) are WHO grade I or II tumors. Pilocytic astrocytoma (PA) is the most common; accounts for 33% of all gliomas in children 0 –14 years and ∼18% of all childhood brain tumors. Prognosis with this slow-growing tumor is excellent; 10 year overall survival of ∼95%. However, event free survival averages ∼50%. Patient age and extent of tumor resection are key prognostic factors; tumor location and size impact resection and outcome.
Brain tumors are the most common solid tumor among children under 15, representing 20% of childhood cancers. Prognosis and therapeutic options vary dramatically based on histologic and molecular profiles. We have studied 222 brain tumors using the CHOP Comprehensive Solid Tumor Panel, which interrogates 238 cancer genes and 110 fusion partners. The most common tumors are pilocytic/pilomyxoid astrocytoma (67), medulloblastoma (23) and diffuse midline glioma (17). Clinically significant genomic alterations were identified in 93% of patients.
Publication date: January–March 2018Source: Saudi Journal of Ophthalmology, Volume 32, Issue 1Author(s): Rita Van Ginderdeuren, Rafael Sciot, Ilse MombaertsAbstractA 11-year-old boy with congenital microphthalmos of the right eye presented with gradual protrusion of his ocular prosthesis. MRI showed an orbital mass adjacent to the microphthalmic eye. After removal of the eye and the orbital soft tissue mass a gliotic mass, resembling a pilocytic astrocytoma WHO grade 1 (glioma) was diagnosed. Through a colobomatous cleft in the eye the tumour spread in the orbit. There were no clinical signs of neurofibromatosis 1. T…
Conditions: Anaplastic Astrocytoma; Glioblastoma; Malignant Glioma Interventions: Radiation: Radiation Therapy; Drug: Temozolomide; Drug: Veliparib Sponsor: National Cancer Institute (NCI) Not yet recruiting