Chromosomal defects track tumor subpopulations and change in progression in oligodendroglioma.
Chromosomal defects track tumor subpopulations and change in progression in oligodendroglioma.
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染色体缺陷追踪肿瘤亚群和少突胶质细胞瘤进展的变化。
DOI：
10.1088/2057-1739/1/1/015001
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Gocke,ChristopherD
中科院分区：
文献类型：
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作者：
Nauen,DavidW;Guajardo,Andrew;Haley,Lisa;Powell,Kerry;Burger,PeterC;Gocke,ChristopherD
为了评估少突胶质细胞瘤 (ODG) 进展中的核型变化和肿瘤亚群，我们使用单核苷酸多态性 (SNP) 微阵列数据分析了组织学诊断的 1p/19q 编码缺失病例。我们根据级别对病例进行分类，对超出 1p/19q 状态的核型信息进行盲分配。 51 个 WHO II 级 (O2) 和 18 个 WHO III 级 (O3) 样本显示出频繁的染色体位置和变化模式，包括 9p 上的杂合性丢失 (LOH)（通常为复制中性）以及 4p 和 4q 上的 LOH。共现分析表明，大多数缺陷是独立的，但也表明在 18、4 和 9 上分别存在缺陷的情况下，11q、13q 和 14q 上出现缺陷的可能性增加。我们使用 B 等位基因频率变化的相对程度作为异常程度的指标，并提供模拟数据来阐明如何推断亚群信息。 9p 缺陷中，89.3% 涉及整个肿瘤，而 4q 缺陷中只有 47.6% 涉及整个肿瘤。我们根据核型变化发生的可能性及其赋予其亚群的适应性对肿瘤的范围进行建模，并使用组数据来估计这些值。为了直接评估进展，我们评估了自 1996 年以来接受多次切除的 6 名患者的标本。其中 4 名患者未接受化疗或放疗，从而可以对肿瘤核型的自然史进行原位评估。第一次切除时整个肿瘤中存在的缺陷仍然如此，而在亚群中，一些缺陷扩大了，一些保持不变，一些消失了。这样做的亚群之间的扩张率并不均匀，并且对适应度的估计可以预测复发时的亚群组成。这些结果扩展了先前关于少突胶质细胞瘤进展过程中核型异常增加的研究，并揭示了肿瘤中亚群随时间的复杂动态。
To assess karyotypic changes and tumor subpopulations in progression of oligodendroglioma (ODG) we analyzed histologically diagnosed 1p/19q codeleted cases using single nucleotide polymorphism (SNP) microarray data. We separated cases according to grade, which was assigned blind to karyotype information beyond 1p/19q status. The 51 WHO grade II (O2) and 18 WHO grade III (O3) specimens showed frequent chromosomal locations and patterns of change including loss of heterozygosity (LOH), often copy-neutral, on 9p and LOH on 4p and 4q together. Analysis of co-occurrence indicated that most defects were independent but also suggested increased likelihood of defects on 11q, 13q, and 14q in the presence of defects on 18, 4, and 9, respectively. We used the relative degree of change in B-allele frequency as an indicator of an abnormality's extent, and we present simulated data to clarify how information on subpopulations was thus inferred. Among 9p defects, 89.3% involved the whole tumor, whereas only 47.6% of 4q defects did so. We modeled extent through the tumor as due to a karyotypic change's likelihood of occurring and the fitness it confers on its subpopulation, and used group data to estimate these values. To assess progression directly, we evaluated specimens from six patients who underwent multiple resections since 1996. Four of these patients had received no chemotherapy or radiation, permitting assessment of the natural history of the tumor karyotype in situ. Defects present throughout a tumor at first resection remained so, whereas among subpopulations, some expanded, some remained constant, and some disappeared. The rate of expansion among subpopulations that did so was not uniform, and estimates of fitness predicted subpopulation composition at recurrence. These results extend prior studies of increased karyotypic abnormality in progression of oligodendroglioma and reveal the complex dynamics of subpopulations in the tumor over time.