Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas.
Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas.
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DOI：
10.1111/j.1750-3639.2012.00630.x
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Rodriguez FJ
中科院分区：
文献类型：
--
作者：
Nguyen DN;Heaphy CM;de Wilde RF;Orr BA;Odia Y;Eberhart CG;Meeker AK;Rodriguez FJ
最近的研究表明，端粒维持机制称为端粒替代性延长（ALT）在特定的胶质瘤亚群中相对更常见，并与ATRX突变密切相关。我们回顾性研究了116例高级别星形细胞瘤（32例儿童胶质母细胞瘤，65例成人胶质母细胞瘤，19例间变性星形细胞瘤），使用组织微阵列确定ALT状态与分子和表型特征的相关性。使用抗ATRX、DAXX、p53和IDH 1 R132 H突变蛋白的抗体进行免疫组织化学。通过FISH评估EGFR扩增。当关注组织学亚型时，几乎一半的星形细胞瘤和双生细胞星形细胞瘤（44%）表现出ALT。相反，所有胶质瘤（n=4）、上皮样瘤（n=2）、巨细胞瘤（n=2）和成人小细胞星形细胞瘤（n=7）均为ALT阴性。ALT表型与圆形细胞（p=0.002）、微囊（p<0.0002）、IDH 1突变蛋白（p<0.0001）、ATRX蛋白缺失（p <0.0001）、P53强表达（p<0.0001）和EGFR扩增缺失（p=0.004）呈正相关。与DAXX表达无显著相关性。我们的结论是ALT代表了高级别星形细胞瘤的一种特殊表型，具有独特的病理和分子特征。未来的研究需要阐明ALT在高级别星形细胞瘤中的临床和生物学意义，以及其作为诊断和/或治疗靶点的可能用途。
Recent studies suggest that the telomere maintenance mechanism known as Alternative Lengthening of Telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas,19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1R132H mutant protein. EGFR amplification was evaluated by FISH. When focusing on histologic subtypes, almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n=4), epithelioid (n=2), giant cell (n=2) and adult small cell astrocytomas (n=7) were ALT negative. The ALT phenotype was positively correlated with the presence of round cells (p=0.002), microcysts (p<0.0002), IDH1 mutant protein (p<0.0001), ATRX protein loss (p<0.0001), strong P53 expression (p<0.0001), and absence of EGFR amplification (p=0.004). There was no significant correlation with DAXX expression. We conclude that ALT represents a specific phenotype in high grade astrocytomas with distinctive pathologic and molecular features. Future studies are required to clarify the clinical and biological significance of ALT in high grade astrocytomas, and its possible utility as a diagnostic and/or therapeutic target.
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影响因子：
12.7
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
6.2
作者：
Perry, A;Aldape, KD;Burger, PC
通讯作者：
Burger, PC
胰腺神经内分泌肿瘤中经常改变DAXX/ATRX，MEN1和MTOR途径基因。
DOI：
10.1126/science.1200609
发表时间：
2011-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jiao Y;Shi C;Edil BH;de Wilde RF;Klimstra DS;Maitra A;Schulick RD;Tang LH;Wolfgang CL;Choti MA;Velculescu VE;Diaz LA Jr;Vogelstein B;Kinzler KW;Hruban RH;Papadopoulos N
通讯作者：
Papadopoulos N
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW