Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping
Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping
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DOI：
10.3171/jns.2000.93.3.0437
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发表时间：
2000-09-01
影响因子：
4.1
通讯作者：
Squire, JA
中科院分区：
文献类型：
--
作者：
Bayani, J;Zielenska, M;Squire, JA
对象。髓母细胞瘤和相关的中枢神经系统原始神经外胚层肿瘤（PNETs）是恶性的、侵袭性的胚胎性肿瘤，以神经元分化为主，占儿童脑肿瘤的20%。细胞遗传学分析表明，17号染色体的改变，特别是17p的缺失和同工染色体17q的形成，以及7号染色体的增加是这组肿瘤中最常见的变化。比较基因组杂交（CGH）研究在很大程度上证实了这些细胞遗传学发现，并确定了新的增益、损失和扩增区域。更复杂的多色荧光原位杂交（FISH）程序的出现，如光谱核型（SKY），现在可以完全识别所有畸变，包括极其复杂的重排。作者报告了19例髓母细胞瘤和5例PNET病例的回顾性分析，采用经典带带分析、FISH、CGH和SKY相结合的方法，全面检查该肿瘤组中存在的染色体畸变，并试图确定常见的结构重排。CGH数据显示，在60%的研究肿瘤中，17q和7号染色体增加，这证实了当前文献报道的数据。然而，作者还结合了所有三种分子细胞遗传学分析的结果（吉姆萨显带、CGH和SKY）来揭示染色体重排的频率（获得、丢失或参与结构重排）。综合结果表明，染色体7和17是重排最多的染色体（在所有检测到的重排中分别占10.1%和8.9%）。3号染色体（7.8%）、14号染色体（7%）、10号染色体（6.7%）、22号染色体（6.5%）、6号染色体（6.5%）、13号染色体（6.2%）、18号染色体（6.2%）重排频繁。24个肿瘤中有8个（33%）表现出高水平的增益或基因扩增。在4个肿瘤中鉴定出MYCN扩增，而在1个肿瘤中鉴定出MYCC扩增。一个肿瘤表现出9p染色体的高水平增加。此外，结缔组织增生髓母细胞瘤和大细胞髓母细胞瘤比传统的髓母细胞瘤表现出更高的核型异质性、扩增性和异常性。
Object. Medulloblastomas and related primitive neuroectodermal tumors (PNETs) of the central nervous system are malignant, invasive embryonal tumors with predominantly neuronal differentiation that comprise 20% of pediatric brain tumors. Cytogenetic analysis has shown that alterations in chromosome 17, particularly the loss of 17p and the formation of isochromosome 17q, as well as the gain of chromosome 7 are the most common changes among this group of tumors. Comparative genomic hybridization (CGH) studies have largely confirmed these cytogenetic findings and have also identified novel regions of gain, loss, and amplification. The advent of more sophisticated multicolored fluorescence in situ hybridization (FISH) procedures such as spectral karyotyping (SKY) now permits complete recognition of all aberrations including extremely complex rearrangements. The authors report a retrospective analysis of 19 medulloblastoma and five PNET cases studied using combinations of classic banding analysis, FISH, CGH, and SKY to examine comprehensively the chromosomal aberrations present in this tumor group and to attempt to identify common structural rearrangement(s).Methods. The CGH data demonstrate gains of chromosomes 17q and 7 in 60% of the tumors studied, which confirms data reported in the current literature. However, the authors have also combined the results of all three molecular cytogenetic assays (Giemsa banding, CGH, and SKY) to reveal the frequency of chromosomal rearrangement (gained, lost, or involved in structural rearrangement).Conclusions. The combined results indicate that chromosomes 7 and 17 are the most frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 10 (6.7%), and 22 (6.5%) were also found to be frequently rearranged, followed by chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tumors exhibited high-level gains or gene amplification. Amplification of MYCN was identified in four tumors, whereas amplification of MYCC was identified in one tumor. One tumor exhibited a high-level gain of chromosome 9p. Additionally, desmoplastic medulloblastomas and large-cell medulloblastomas exhibited higher karyotype heterogeneity, amplification, and aneusomy than classic medulloblastomas.