Holland Heidrun, Koschny Ronald, Krupp Wolfgang, Meixensberger Jürgen, Bauer Manfred, Schober Ralf, Kirsten Holger, Ganten Tom M, Ahnert Peter
Biotechnical-Biomedical Center (BBZ) and Institute of Clinical Immunology and Transfusion Medicine, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
Cancer Genet Cytogenet. 2007 Oct 15;178(2):104-13. doi: 10.1016/j.cancergencyto.2007.06.005.
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.
髓母细胞瘤是一种恶性侵袭性胚胎性肿瘤，主要发生于儿童。在成人中较为罕见（占成人脑肿瘤的比例<1%），因此关于成人髓母细胞瘤的全面细胞遗传学和分子生物学数据非常有限。传统疗法的长期疾病控制效果令人失望，新的治疗方案正在进行测试。我们对一例世界卫生组织IV级成人髓母细胞瘤进行了全面的细胞遗传学分析，采用胰蛋白酶-吉姆萨染色（GTG显带）、多色荧光原位杂交（M-FISH）和位点特异性FISH，并辅以使用高密度单核苷酸多态性（SNP）阵列的分子核型分析。对25个中期细胞进行GTG显带分析发现了31个结构染色体畸变，主要位于4号染色体长臂、9号染色体长臂、10号染色体长臂、11号染色体短臂和20号染色体长臂，这些结果经M-FISH证实。发现了两个新的、迄今为止未描述的易位：t(4;11)(q25;p15)和t(9;20)(p23;p12)。GTG显带、位点特异性FISH和M-FISH检测到8号、14号、18号、19号、20号、21号和22号染色体的数目变化。通过SNP阵列进行的分子核型分析证实了染色体改变-2p、-10q、-16q和-Xq，并发现了新发的1号染色体长臂和9号染色体长臂部分单亲二体。应用一种即将出现的治疗方法，我们发现原发性髓母细胞瘤细胞对新型抗癌细胞因子TRAIL具有抗性，但与蛋白酶体抑制剂硼替佐米联合治疗可有效使其致敏。硼替佐米-TRAIL联合治疗可能是髓母细胞瘤患者的一种有效治疗选择。
