Intratumoral cytogenetic heterogeneity detected by comparative genomic hybridization and laser scanning cytometry in human gliomas.
Intratumoral cytogenetic heterogeneity detected by comparative genomic hybridization and laser scanning cytometry in human gliomas.
复制标题
通过比较基因组杂交和激光扫描细胞术检测人胶质瘤的瘤内细胞遗传学异质性。
作者：
K. Harada;T. Nishizaki;S. Ozaki;H. Kubota;Haruhide Ito;Kohsuke Sasaki
尽管众所周知，癌症表现出瘤内表型异质性，但基因型研究却很少。使用比较基因组杂交和激光扫描细胞计数分析，我们研究了 21 例手术切除的神经胶质瘤的瘤内细胞遗传学异质性，其中包括 11 例胶质母细胞瘤 (GBM)、8 例间变性星形细胞瘤 (AA) 和 2 例低级别星形细胞瘤。比较基因组杂交分析显示，在高级星形细胞瘤中，63% 获得或扩增 7p，73% 获得 7q，53% 获得 9p，47% 获得 10p，47% 获得 10q，53% 获得 13q，37% 获得 22q。由于这些畸变在同一肿瘤内是区域无关的，因此它们不会导致肿瘤内细胞遗传学异质性。这种异质性是由于除上述区域无关的畸变之外的细胞遗传学变化所致。在 11 个 GBM 中的 8 个、8 个 AA 中的 4 个和 2 个低级别星形细胞瘤中均未检测到瘤内细胞遗传学异质性。这些观察结果表明，7、9p、10、13 和 22 号染色体的细胞遗传学变化是高级别星形细胞瘤的主要事件，随后涉及拷贝数增加的细胞遗传学变化提供了肿瘤内异质性。通过激光扫描细胞术在 11 个 GBM 中的 5 个和 8 个 AA 中的 1 个中检测到 DNA 非整倍性。所有具有DNA非整倍性的肿瘤均表现出瘤内细胞遗传学异质性，并且DNA非整倍性与瘤内细胞遗传学异质性之间存在显着相关性。这些结果支持这样的观点：细胞遗传学异质性是由肿瘤内的遗传不稳定性造成的。
Although it is well-known that cancers show intratumoral phenotypic heterogeneity, genotypic studies have been scarce. Using comparative genomic hybridization and laser scanning cytometric analyses, we investigated intratumoral cytogenetic heterogeneity in 21 surgically removed gliomas including 11 glioblastomas (GBMs), 8 anaplastic astrocytomas (AAs) and 2 low-grade astrocytomas. Comparative genomic hybridization analysis revealed gain or amplification of 7p in 63%, gain of 7q in 73%, loss of 9p in 53%, loss of 10p in 47%, loss of 10q in 47%, loss of 13q in 53%, and loss of 22q in 37% of high-grade astrocytomas. Because these aberrations were region-independent within the same tumor, they did not contribute to intratumoral cytogenetic heterogeneity. Such heterogeneity was due to cytogenetic changes other than the above region-independent aberrations. Intratumoral cytogenetic heterogeneity was detected in 8 of 11 GBMs, 4 of 8 AAs, and none of the 2 low-grade astrocytomas. These observations suggest that cytogenetic changes at chromosomes 7, 9p, 10, 13, and 22 are primary events in high-grade astrocytomas and that subsequent cytogenetic changes involving increases in copy number provide intratumoral heterogeneity. DNA aneuploidy was detected by laser scanning cytometry in 5 of 11 GBMs and 1 of 8 AAs. All tumors with DNA aneuploidy exhibited intratumoral cytogenetic heterogeneity, and there was a significant correlation between DNA aneuploidy and intratumoral cytogenetic heterogeneity. These results support the notion that cytogenetic heterogeneity results from genetic instability within a tumor.