Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
Pathol Res Pract. 2013 Sep;209(9):541-7. doi: 10.1016/j.prp.2013.06.001. Epub 2013 Jul 4.
Medulloblastoma (WHO grade IV) is a rare, malignant, invasive, embryonal tumor which mainly occurs in children and represents less than 1% of all adult brain tumors. Systematic comprehensive genetic analyses on medulloblastomas are rare but necessary to provide more detailed information. Therefore, we performed comprehensive cytogenetic analyses (blood and tissue) of two pediatric and one adult medulloblastoma, using trypsin-Giemsa staining, spectral karyotyping (tissues only), SNP-arrays, and gene expression analyses. We confirmed frequently detected chromosomal aberrations in medulloblastoma, such as +7q, -8p/q, -9q, -11q, -12q, and +17q and identified novel genetic events. Applying SNP-array, we identified constitutional de novo losses 5q21.1, 15q11.2, 17q21.31, 19p12 (pediatric medulloblastoma), 9p21.1, 19p12, 19q13.3, 21q11.2 (adult medulloblastoma) and gains 16p11.1-16p11.2, 18p11.32, Yq11.223-Yq11.23 (pediatric medulloblastoma), Xp22.31 (adult medulloblastoma) possibly representing inherited causal events for medulloblastoma formation. We show evidence for somatic segmental uniparental disomy in regions 1p36, 6q16.3, 6q24.1, 14q21.2, 17p13.3, and 17q22 not previously described for primary medulloblastoma. Gene expression analysis supported classification of the adult medulloblastoma to the WNT-subgroup and classification of pediatric medulloblastomas to group 3 tumors. Analyses of tumors and matched normal tissues (blood) with a combination of complementary techniques will help to further elucidate potentially causal genetic events for medulloblastomas.
髓母细胞瘤（WHO 分级 IV）是一种罕见的、恶性的、侵袭性的胚胎肿瘤，主要发生在儿童中，占所有成人脑肿瘤的不到 1%。对髓母细胞瘤进行系统全面的遗传分析很少见，但却是提供更详细信息所必需的。因此，我们对两个小儿和一个成人髓母细胞瘤进行了综合细胞遗传学分析（血液和组织），使用胰蛋白酶-Giemsa 染色、光谱核型分析（仅组织）、SNP 阵列和基因表达分析。我们证实了髓母细胞瘤中经常检测到的染色体异常，如 +7q、-8p/q、-9q、-11q、-12q 和 +17q，并鉴定了新的遗传事件。应用 SNP 阵列，我们鉴定了小儿髓母细胞瘤中存在的新生性缺失 5q21.1、15q11.2、17q21.31、19p12，成人髓母细胞瘤中存在的缺失 9p21.1、19p12、19q13.3、21q11.2，以及小儿髓母细胞瘤中存在的增益 16p11.1-16p11.2、18p11.32、Yq11.223-Yq11.23，成人髓母细胞瘤中存在的增益 Xp22.31，这些可能代表髓母细胞瘤形成的遗传性因果事件。我们证明了 1p36、6q16.3、6q24.1、14q21.2、17p13.3 和 17q22 区域的体细胞片段单亲二体性，这些区域以前没有被描述为原发性髓母细胞瘤。基因表达分析支持成人髓母细胞瘤分类为 WNT 亚组，小儿髓母细胞瘤分类为 3 组肿瘤。综合运用互补技术对肿瘤和匹配的正常组织（血液）进行分析，将有助于进一步阐明髓母细胞瘤的潜在因果遗传事件。
