Cytogenetic and molecular biological characterization of an adult medulloblastoma.
Medulloblastoma is a malignant invasive embryonal tumor, occurring in children mainly. It is rare in adults (<1% of adult brain tumors), and so comprehensive cytogenetic and molecular biological data on adult medulloblastomas are very limited. Conventional therapies provide disappointing long-term disease control, and new therapeutic options are being tested. We performed comprehensive cytogenetic analyses of an adult medulloblastoma, WHO grade IV, using trypsin-Giemsa staining (GTG-banding), multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH, complemented by molecular karyotyping using high-density single nucleotide polymorphism (SNP) arrays. GTG-banding of 25 metaphases revealed 31 structural chromosomal aberrations, predominantly located on chromosomes 4q, 9q, 10q, 11p, and 20q, which were confirmed by M-FISH. Two novel, so far not described translocations were found: t(4;11)(q25;p15) and t(9;20)(p23;p12). GTG-banding, locus-specific FISH, and M-FISH detected numerical changes of chromosomes 8, 14, 18, 19, 20, 21, and 22. Molecular karyotyping by SNP array confirmed chromosomal changes -2p, -10q, -16q, and -Xq and revealed de novo partial uniparental disomy 1q and 9q. Applying an upcoming therapeutic approach, we found that primary medulloblastoma cells were resistant to TRAIL, a novel anticancer cytokine, but could be efficiently sensitized by cotreatment with the proteasome inhibitor bortezomib. Bortezomib-TRAIL cotreatment may serve as a powerful therapeutic option for medulloblastoma patients.
Holland
Heidrun
H
Biotechnical-Biomedical Center (BBZ) and Institute of Clinical Immunology and Transfusion Medicine, Faculty of Medicine, University of Leipzig, Leipzig, Germany. heidrun.holland@medizin.uni-leipzig.de
Koschny
Ronald
R
Krupp
Wolfgang
W
Meixensberger
Jürgen
J
Bauer
Manfred
M
Schober
Ralf
R
Kirsten
Holger
H
Ganten
Tom M
TM
Ahnert
Peter
P
D000328:Adult; D002528:Cerebellar Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D008527:Medulloblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016708:Synaptophysin / Q000235:genetics
D016708:Synaptophysin; D020778:Matrix Metalloproteinase 2; D010751:Phosphopyruvate Hydratase