Diagnostic utility of telomere length testing in a hospital-based setting

Alder Jonathan K.; Hanumanthu Vidya Sagar; Strong Margaret A.DeZern Amy E.Stanley Susan E.Takemoto Clifford M.Danilova LudmillaApplegate Carolyn D.Bolton Stephen G.Mohr David W.Brodsky Robert A.Casella James F.Greider Carol W.Jackson J. BrooksArmanios Mary

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Diagnostic utility of telomere length testing in a hospital-based setting

机译：Diagnostic utility of telomere length testing in a hospital-based setting

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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 agedependent, 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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《Proceedings of the National Academy of Sciences of the United States of America.》 |2018年第10期|E2358-E2365|共8页
作者
Alder Jonathan K.; Hanumanthu Vidya Sagar; Strong Margaret A.DeZern Amy E.Stanley Susan E.Takemoto Clifford M.Danilova LudmillaApplegate Carolyn D.Bolton Stephen G.Mohr David W.Brodsky Robert A.Casella James F.Greider Carol W.Jackson J. BrooksArmanios Mary;
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作者单位

Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA;

Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA;

Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USAJohns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USAJohns Hopkins Univ, Sch Med, Telomere Ctr Johns Hopkins, Baltimore, MD 21287 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
aplastic anemia; interstitial lung disease; primary immunodeficiency; liver disease; precision medicine;

Diagnostic utility of telomere length testing in a hospital-based setting

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