PubMed · 13113080
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A EDERLI, V BRAITENBERG. [Diffuse astrocytomas].. https://pubmed.ncbi.nlm.nih.gov/13113080/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Identification of distinct molecular subtypes is a critical challenge for cancer biology. In this study, we used Affymetrix high-density oligonucleotide arrays to identify the global gene expression signatures associated with gliomas of different types and grades. Here, we show that the global transcriptional profiles of gliomas of different types and grades are distinct from each other and from the normal brain. To determine whether our data could be used to uncover molecular subtypes without prior knowledge of pathologic type and grade, we performed K-means clustering analysis and found evidence for three clusters with the aid of multidimensional scaling plots. These clusters corresponded to glioblastomas, lower grade astrocytomas and oligodendrogliomas (P<0.00001). A predictor constructed from the 170 genes that are most differentially expressed between the subsets correctly identified the type and grade of all samples, indicating that a relatively small number of genes can be used to distinguish between these molecular subtypes. These results further define molecular subsets of gliomas which may potentially be used for patient stratification, and suggest potential targets for treatment.
BACKGROUND: In an era of organ shortage, the use of expanded or marginal donors has been attempted to increase transplantation rates and diminish waiting list mortality. One strategy is the use of organs from patients with a history of or active central nervous system (CNS) tumor. METHODS: Sixty-two recipients were identified as the recipients of organs from donors with a history of or active CNS malignancy. Patient demographics, donor tumor management, incidence of tumor transmission, and patient survival were examined. RESULTS: Of the organs recovered and transplanted from donors with astrocytoma, 14 were associated with at least one risk factor including high-grade tumor (n=4), prior surgery (n=5), radiation therapy (n=4), and systemic chemotherapy (n=4). One tumor transmission was identified at 20 months posttransplant with the patient expiring from metastatic disease. Twenty-six organs were transplanted from glioblastoma patients with 15 demonstrating risk factors including high-grade tumor (n=9) and prior surgery (n=10). Eight transmissions were identified with a range of 2 to 15 months posttransplant, with seven patients dying as the result of metastatic disease. Seven organs were used from donors with a medulloblastoma. Three transmissions were identified at a range of 5 to 7 months, all associated with ventriculoperitoneal shunts. Two medulloblastoma recipients died as the result of metastatic disease, whereas the third is alive with diffuse disease. The rate of donor tumor transmission, in the absence of risk factors, was 7%, whereas in the presence of one or more risk factor this rate dramatically rose to 53% (P<0.01). CONCLUSIONS: Organs from donors with CNS tumors can be used with a low risk of donor tumor transmission in the absence of the following risk factors: high-grade tumors, ventriculoperitoneal or ventriculoatrial shunts, prior craniotomy, and systemic chemotherapy.
In humans and gene-targeted mice, loss of multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene function causes neuroendocrine tumors, frequently of the parathyroid and pituitary glands and the pancreas. The MEN1 gene product interacts with glial fibrillary acidic protein (GFAP) in the brain. We here demonstrate bi-allelic MEN1 inactivation in a grade II astrocytoma in an individual carrying a heterozygous MEN1 germ line deletion mutation (788del6). This tumor represents a novel, non-endocrine MEN1-phenotype, compatible with a role of MEN1-GFAP in glial oncogenesis. Clinically, a genetic predisposition to variant neoplasias should be considered in the management of MEN1 patients.