LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR).

LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR).
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DOI:
10.1007/s00401-012-1068-3
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发表时间:
2012-12
影响因子:
12.7
通讯作者:
Kool M
Kool M
中科院分区:
医学1区
文献类型:
--
作者:
Korshunov A;Ryzhova M;Jones DT;Northcott PA;van Sluis P;Volckmann R;Koster J;Versteeg R;Cowdrey C;Perry A;Picard D;Rosenblum M;Giangaspero F;Aronica E;Schüller U;Hasselblatt M;Collins VP;von Deimling A;Lichter P;Huang A;Pfister SM;Kool M

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胚胎性肿瘤伴多层结节(ETMR,以前称为ETANTR)是一种高度侵袭性的胚胎性中枢神经系统肿瘤,几乎只影响婴儿,预后不良。准确的诊断是至关重要的临床重要性,因为它的反应差,目前的治疗方案和其独特的生物学。19q13.42处的miRNA簇的扩增先前已被鉴定为ETMR的遗传标志,但仍然缺乏用于临床常规诊断的基于化学的测定[例如用于非典型畸胎样横纹肌样肿瘤(AT/RT)的INI-1]。在这项研究中,我们使用超过1,400个脑肿瘤的基因表达谱数据集筛选ETMR特异性标志物,并将LIN 28 A鉴定为ETMR的高度特异性标志物。编码的蛋白质结合小RNA,并与干细胞多能性、代谢和肿瘤发生有关。使用LIN 28 A特异性抗体,我们对800多例儿童脑肿瘤样本中的LIN 28 A进行了免疫组化分析,证实了其对ETMR的高特异性。在所有37个测试的ETMR样品中发现了强LIN 28 A免疫表达,而局灶反应性仅存在于小比例(6/50)的AT/RT样品中。所有其他儿科脑肿瘤均为LIN 28 A阴性。总之,我们建立了LIN 28 A免疫组织化学作为一种高度敏感和特异性,快速,廉价的诊断工具,用于常规病理验证ETMR。
Embryonal tumor with multilayered rosettes (ETMR, previously known as ETANTR) is a highly aggressive embryonal CNS tumor, which almost exclusively affects infants and is associated with a dismal prognosis. Accurate diagnosis is of critical clinical importance because of its poor response to current treatment protocols and its distinct biology. Amplification of the miRNA cluster at 19q13.42 has been identified previously as a genetic hallmark for ETMR, but an immunohistochemistry-based assay for clinical routine diagnostics [such as INI-1 for atypical teratoid rhabdoid tumor (AT/RT)] is still lacking. In this study, we screened for an ETMR-specific marker using a gene-expression profiling dataset of more than 1,400 brain tumors and identified LIN28A as a highly specific marker for ETMR. The encoded protein binds small RNA and has been implicated in stem cell pluripotency, metabolism and tumorigenesis. Using an LIN28A specific antibody, we carried out immunohistochemical analysis of LIN28A in more than 800 childhood brain-tumor samples and confirmed its high specificity for ETMR. Strong LIN28A immunoexpression was found in all 37 ETMR samples tested, whereas focal reactivity was only present in a small (6/50) proportion of AT/RT samples. All other pediatric brain tumors were completely LIN28A-negative. In summary, we established LIN28A immunohistochemistry as a highly sensitive and specific, rapid, inexpensive diagnostic tool for routine pathological verification of ETMR.
DOI: 10.1038/modpathol.2010.195
发表时间: 2011-02-01
期刊: MODERN PATHOLOGY
影响因子: 7.5
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Cao, Dengfeng;Liu, Aijun;Li, Jianping
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DOI: 10.1200/jco.2011.35.5677
发表时间: 2011-10-20
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发表时间: 2011-12-01
期刊: NEURO-ONCOLOGY
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DOI: 10.1200/jco.2009.26.7252
发表时间: 2010-06-20
影响因子: 45.3
作者:
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DOI: 10.1007/s10048-006-0032-6
发表时间: 2006-05-01
期刊: NEUROGENETICS
影响因子: 2.2
作者:
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通讯作者: Zlotnik, A