Cytogenetic and molecular biological characterization of an adult medulloblastoma

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• 作者：Heidrun Holl ; Ronald Koschny ; Wolfgang Krupp ; Jü ; rgen Meixensberger ; Manfred Bauer ; Ralf Schober ; Holger Kirsten ; Tom M. Ganten ; Peter Ahnert
• 关键词：Antibacterial ; Skin graft ; Fixation ; Infection ; Graft reject
• 刊名：Cancer Genetics and Cytogenetics
• 出版年：2007
• 出版时间：15 October 2007
• 年：2007
• 卷：178
• 期：2
• 页码：104-113
• 全文大小：774 K

文摘

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.