Cell-to-cell Variation of Chromosomal Number in the Adult Testicular Germ Cell Tumors: A Comparison of Chromosomal Instability Among Histological Components and Its Putative Role in Tumor Progression
Cell-to-cell Variation of Chromosomal Number in the Adult Testicular Germ Cell Tumors: A Comparison of Chromosomal Instability Among Histological Components and Its Putative Role in Tumor Progression
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成体睾丸生殖细胞肿瘤中染色体数目的细胞间变异：组织学成分之间染色体不稳定性的比较及其在肿瘤进展中的假定作用
DOI：
10.1007/s00428-019-02560-6
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发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Tsuda H.
中科院分区：
文献类型：
--
作者：
Miyai K;Ito K;Nakanishi K;Tsuda H.
通过等位基因型分析，我们之前报道了混合型睾丸生殖细胞肿瘤（TGCT）中从生殖细胞原位肿瘤（GCNIS）到精原细胞瘤，然后到胚胎癌的假定进展途径，并检测到混合肿瘤中精原细胞瘤成分的杂合性丢失事件比纯精原细胞瘤中的杂合性丢失事件更频繁。为了阐明染色体不稳定性在非精原细胞生殖细胞肿瘤 (NSGCT) 进展中的作用，我们使用染色体 1、7、8、12、17 和 X 的着丝粒探针对 52 例 TGCT 病例进行了荧光原位杂交，其中 103 个组织学上不同的成分：39 个 GCNIS 病变（有和没有 NSGCT 的肿瘤中分别有 16 个和 23 个）分别）、39 例精原细胞瘤（27 例为纯精原细胞瘤，12 例为混合瘤）和 25 例胚胎癌。在总成分的基础上，从 GCNIS 到精原细胞瘤，再到胚胎癌，每个肿瘤细胞核的平均拷贝数和与所有检查的染色体模数的偏差都显着增加，几乎没有例外。混合肿瘤中的精原细胞瘤成分显示出 8 号和 12 号染色体的染色体不稳定性显着高于纯精原细胞瘤，而具有和不具有 NSGCT 成分的 GCNIS 病变之间没有观察到统计学上的显着差异。这些结果表明，不仅非整倍性，而且细胞间染色体数量的变异也是染色体不稳定的敏感指标，并且与 NSGCT 的进展有关。
By allelotyping analysis, we previously reported a putative progression pathway from germ cell neoplasia in situ (GCNIS) to seminoma, then to embryonal carcinoma in mixed-type testicular germ cell tumors (TGCTs), and detected that loss of heterozygosity events in seminoma components in mixed tumors were more frequent than those in pure seminomas. To elucidate a role of chromosomal instability in the progression of non-seminomatous germ cell tumor (NSGCT), we performed fluorescence in situ hybridization with centromeric probes for chromosomes 1, 7, 8, 12, 17, and X on a cohort of 52 TGCT cases with 103 histologically distinct components: 39 GCNIS lesions (16 and 23 in tumors with and without NSGCT components, respectively), 39 seminomas (27 as pure seminomas and 12 in mixed tumors), and 25 embryonal carcinomas. On a total component basis, both the mean copy number per tumor cell nucleus and the deviations from the modal number of all chromosomes examined significantly increased from GCNIS to seminoma, then to embryonal carcinoma with few exceptions. Seminoma components in mixed tumors showed a significantly greater extent of chromosomal instability in chromosomes 8 and 12 than pure seminomas, whereas no statistically significant difference was observed between GCNIS lesions with and without NSGCT components. These results suggest that not only aneuploidy, but also the cell-to-cell variation of chromosomal number is a sensitive indicator of chromosomal instability and would be implicated in the progression of NSGCT.