神经纤维瘤病 1 型相关实体瘤中的端粒改变。
Telomere alterations in neurofibromatosis type 1-associated solid tumors.
机构信息
Departments of Pathology, Johns Hopkins University School of Medicine, Sheikh Zayed Tower, Room M2101, 1800 Orleans Street, Baltimore, MD, 21231, USA.
Departments of Ophthalmology, Johns Hopkins University School of Medicine, Sheikh Zayed Tower, Room M2101, 1800 Orleans Street, Baltimore, MD, 21231, USA.
出版信息
Acta Neuropathol Commun. 2019 Aug 28;7(1):139. doi: 10.1186/s40478-019-0792-5.
The presence of Alternative lengthening of telomeres (ALT) and/or ATRX loss, as well as the role of other telomere abnormalities, have not been formally studied across the spectrum of NF1-associated solid tumors. Utilizing a telomere-specific FISH assay, we classified tumors as either ALT-positive or having long (without ALT), short, or normal telomere lengths. A total of 426 tumors from 256 NF1 patients were evaluated, as well as 99 MPNST tumor samples that were sporadic or of unknown NF1 status. In the NF1-glioma dataset, ALT was present in the majority of high-grade gliomas: 14 (of 23; 60%) in contrast to only 9 (of 47; 19%) low-grade gliomas (p = 0.0009). In the subset of ALT-negative glioma cases, telomere lengths were estimated and we observed 17 (57%) cases with normal, 12 (40%) cases with abnormally long, and only 1 (3%) case with short telomeres. In the NF1-associated malignant nerve sheath tumor (NF1-MPNST) set (n = 75), ALT was present in 9 (12%). In the subset of ALT-negative NF1-MPNST cases, telomeres were short in 9 (38%), normal in 14 (58%) and long in 1 (3%). In the glioma set, overall survival was significantly decreased for patients with ALT-positive tumors (p < 0.0001). In the NF1-MPNST group, overall survival was superior for patients with tumors with short telomeres (p = 0.003). ALT occurs in a subset of NF1-associated solid tumors and is usually restricted to malignant subsets. In contrast, alterations in telomere lengths are more prevalent than ALT.
端粒的非经典延长（ALT）和/或 ATRX 缺失的存在，以及其他端粒异常的作用，尚未在 NF1 相关实体瘤谱中进行正式研究。我们利用端粒特异性 FISH 检测，将肿瘤分为 ALT 阳性或具有长（无 ALT）、短或正常端粒长度的肿瘤。共评估了 256 例 NF1 患者的 426 个肿瘤，以及 99 个散发性或 NF1 状态未知的 MPNST 肿瘤样本。在 NF1-神经胶质瘤数据集中，ALT 存在于大多数高级别神经胶质瘤中：23 例中的 14 例（60%），而低级别神经胶质瘤中仅 9 例（47%）（p=0.0009）。在 ALT 阴性神经胶质瘤病例亚组中，估计了端粒长度，我们观察到 17 例（57%）正常，12 例（40%）异常长，仅 1 例（3%）短。在 NF1 相关恶性神经鞘瘤（NF1-MPNST）组（n=75）中，ALT 阳性 9 例（12%）。在 ALT 阴性 NF1-MPNST 病例亚组中，9 例（38%）端粒短，14 例（58%）端粒正常，1 例（3%）端粒长。在神经胶质瘤组中，ALT 阳性肿瘤患者的总生存率显著降低（p<0.0001）。在 NF1-MPNST 组中，端粒短的肿瘤患者总生存率更好（p=0.003）。ALT 发生在 NF1 相关实体瘤的一个亚组中，通常局限于恶性亚组。相比之下，端粒长度的改变比 ALT 更为普遍。
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