Diagnostic utility of telomere length testing in a hospital-based setting.
Diagnostic utility of telomere length testing in a hospital-based setting.
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DOI：
10.1073/pnas.1720427115
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发表时间：
2018-03-06
影响因子：
11.1
通讯作者：
Armanios M
中科院分区：
文献类型：
--
作者：
Alder JK;Hanumanthu VS;Strong MA;DeZern AE;Stanley SE;Takemoto CM;Danilova L;Applegate CD;Bolton SG;Mohr DW;Brodsky RA;Casella JF;Greider CW;Jackson JB;Armanios M
这项研究定义了在医院环境中使用端粒长度 (TL) 测量作为诊断工具的临床适应症。它表明，与其他方法相比，通过流式细胞术和荧光原位杂交（flowFISH）进行的TL测量可以标准化，并且具有可重复和可定义的正常上限和下限。在端粒酶突变携带者和其他突变端粒维持基因携带者中，TL具有预后价值，与短端粒综合征表型的发病年龄以及主要并发症相关。在一项前瞻性研究中，TL 结果对四分之一影响干细胞捐献者选择和/或治疗方案的特发性骨髓衰竭病例是可行的。数据显示，对于有针对性的临床适应症，在医院环境中，flowFISH 的 TL 测量可为患者护理决策提供信息。端粒长度 (TL) 可预测体外细胞衰老的发生，但 TL 测量在临床环境中的诊断效用尚不完全清楚。我们通过流式细胞术和荧光原位杂交（flowFISH）测试了端粒酶和端粒维持基因突变患者的 TL 测量值。 TL 具有离散且可重复的正常范围，具有可定义的上限和下限。虽然高于第 50 个年龄调整百分位数的 TL 对于临床相关突变具有 100% 阴性预测值，但突变携带者的下限阈值取决于年龄，并且成人突变携带者通常与最低十分位数的对照重叠。端粒缩短的程度与诊断时的年龄以及短端粒综合征表型相关。极短的 TL 会导致儿童和年轻人的骨髓衰竭和免疫缺陷，而较轻微的缺陷则在成人中表现为肺纤维化-肺气肿。我们前瞻性地研究了 TL 是否改变了新诊断的特发性骨髓衰竭患者的治疗决策，发现除了端粒酶和端粒维持基因外，一些遗传性骨髓衰竭基因（例如 RUNX1）突变的患者的 TL 异常短。结果是可行的，在四分之一的病例中改变了治疗方案和/或造血干细胞捐献者的选择（38 例中的 9 例，24%）。我们的结论是，当用于有针对性的临床适应症和在有限的环境中时，flowFISH 的 TL 测量可以以改善结果的方式影响治疗决策。
This study defines clinical indications for using telomere length (TL) measurement as a diagnostic tool in a hospital setting. It shows that, in contrast to other methods, TL measurement by flow cytometry and FISH (flowFISH) can be standardized, and has reproducible and definable upper and lower normal boundaries. In telomerase mutation carriers and carriers of other mutant telomere maintenance genes, TL had prognostic value, correlating with the age of onset of short telomeres syndrome phenotypes, as well as the predominant complication. In a prospective study, TL results were actionable in one-fourth of cases with idiopathic bone marrow failure affecting the stem cell donor choice and/or treatment regimen. The data show that, for targeted clinical indications, and in a hospital setting, TL measurement by flowFISH informs patient care decisions. Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries. While TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations, the lower threshold in mutation carriers was age-dependent, and adult mutation carriers often overlapped with the lowest decile of controls. The extent of telomere shortening correlated with the age at diagnosis as well as the short telomere syndrome phenotype. Extremely short TL caused bone marrow failure and immunodeficiency in children and young adults, while milder defects manifested as pulmonary fibrosis-emphysema in adults. We prospectively examined whether TL altered treatment decisions for newly diagnosed idiopathic bone marrow failure patients and found abnormally short TL enriched for patients with mutations in some inherited bone marrow failure genes, such as RUNX1, in addition to telomerase and telomere maintenance genes. The result was actionable, altering the choice of treatment regimen and/or hematopoietic stem cell donor in one-fourth of the cases (9 of 38, 24%). We conclude that TL measurement by flowFISH, when used for targeted clinical indications and in limited settings, can influence treatment decisions in ways that improve outcome.
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影响因子：
4.5
作者：
Aubert G;Baerlocher GM;Vulto I;Poon SS;Lansdorp PM
通讯作者：
Lansdorp PM
影响因子：
14.9
作者：
Cawthon RM
通讯作者：
Cawthon RM
DOI：
10.1038/nrg3246
发表时间：
2012-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
168.9
作者：
Fogarty, PF;Yamaguchi, H;Young, NS
通讯作者：
Young, NS