目的探讨H3.3G34W、p63及SATB2在骨巨细胞瘤(giant cell tumor of bone,GCTB)中的表达情况及其联合应用对GCTB的诊断作用和价值。方法收集西安交通大学附属红会医院病理科2020年至2022年诊断的54例GCTB、83例非骨巨细胞瘤(non-giant cel...目的探讨H3.3G34W、p63及SATB2在骨巨细胞瘤(giant cell tumor of bone,GCTB)中的表达情况及其联合应用对GCTB的诊断作用和价值。方法收集西安交通大学附属红会医院病理科2020年至2022年诊断的54例GCTB、83例非骨巨细胞瘤(non-giant cell tumor of bone,NGCTB)(包含14例动脉瘤样骨囊肿、16例软骨母细胞瘤和53例非骨化性纤维瘤)患者的样本和病历资料,采用免疫组织化学EliVision法检测H3.3G34W、p63及SATB2的表达情况。通过χ^(2)检验判断H3.3G34W、p63及SATB2的阳性率在各组间是否存在统计学差异;通过Logistic回归分析建立包括H3.3G34W、p63及SATB2的联合诊断模型,通过受试者工作特征(ROC)曲线分析评价模型的诊断价值。结果H3.3G34W、p63及SATB2在GCTB组中阳性率分别为81.5%、90.7%、92.6%;在NGCTB组中阳性率分别为2.4%、28.9%、62.7%。与NGCTB组相比,GCTB组患者年龄显著较大[(41.222±14.849)vs.(16.566±9.439);P<0.001],女性比男性患病率更高(51.9%vs.48.1%,P<0.001)。与NGCTB组相比,GCTB组中H3.3G34W(81.5%vs.2.4%,P<0.001);p63(90.7%vs.28.9%,P<0.001)和SATB2(92.6%vs.62.7%,P<0.001)的阳性率更高。单因素Logistic回归分析构建单因素预测模型,同时行ROC曲线分析,表明年龄(AUC=92.9%,P<0.001)、性别(AUC=64.5%,P=0.004)、H3.3G34W阳性率(AUC=89.5%,P<0.001)、p63阳性率(AUC=80.9%,P<0.001)、SATB2阳性率(AUC=65.0%,P=0.003)是GCTB诊断的独立预测因素。进一步的多因素Logistic回归分析构建混合预测模型,并行ROC曲线分析,发现混合模型展现出比单因素模型更好的预测价值(AUC=98.4%,P<0.001)。结论H3.3G34W、p63及SATB2是有效诊断GCTB的分子标记物,且三者联合应用更能提高GCTB的诊断预测效能。展开更多
Histone point mutations,including missense mutations on histone H3 at positions 27(K27M),34(G34R/V,G34W,G34L)and 36(K36M),were identified as potential cancer driver mutations.H3.3G34R/V mutations account for pediatric...Histone point mutations,including missense mutations on histone H3 at positions 27(K27M),34(G34R/V,G34W,G34L)and 36(K36M),were identified as potential cancer driver mutations.H3.3G34R/V mutations account for pediatric glioblastomas(GBM).RACK7(also known as ZMYND8,PRKCBP1)was recently reported to specifically bind H3.3G34R through its PHD(plant homedomain)domain(PHDRACK7)in vitro and in H3.3G34R pediatric glioblastoma cells,playing key roles in H3.3G34R-mediated gene transcription.Herein,we provided both biochemical and NMR structural evidences that PHDRACK7 recognized histone H3.3G34R mutant via a mechanism distinet from all other reported PHD domains.Except the reported residue D104,two new sites D108 and L121 of PHD^(RACK7) were found necessary for the interactions between PHD^(RACK7) and histone H3.3G34R peptide.Our results provided a potential molecular basis for pediatric GBM driven by the H3.3G34R mutation.展开更多
Histones are the main protein components of eukaryotic chromatin. Histone variants and histone modifications modulate chromatin structure, ensuring the precise operation of cellular processes associated with genomic D...Histones are the main protein components of eukaryotic chromatin. Histone variants and histone modifications modulate chromatin structure, ensuring the precise operation of cellular processes associated with genomic DNA. H3.3, an ancient and conserved H3 variant, differs from its canonical H3 counterpart by only five amino acids, yet it plays essential and specific roles in gene transcription, DNA repair and in maintaining genome integrity. Here, we review the most recent insights into the functions of histone H3.3, and the involvement of its mutant forms in human diseases.展开更多
骨巨细胞瘤 (giant cell tumor of bone,GCTB)是发生在骨关节骺端的一种常见的交界性肿瘤,具有局部复发性以及罕见远处转移可能,很少发生恶性变。骨巨细胞瘤中的恶性肿瘤 (malignancy in giant cell tumor of bone,MGCTB),也就是过去称...骨巨细胞瘤 (giant cell tumor of bone,GCTB)是发生在骨关节骺端的一种常见的交界性肿瘤,具有局部复发性以及罕见远处转移可能,很少发生恶性变。骨巨细胞瘤中的恶性肿瘤 (malignancy in giant cell tumor of bone,MGCTB),也就是过去称谓的恶性骨巨细胞瘤,在骨巨细胞瘤中含有高级别肉瘤成分。依据最初诊断时就证实同时存在高级别肉瘤成分.展开更多
From the perspective of growth units, the growth mechanism of Mg2（OH）2CO3.3H2O whisker is investigated in this paper. Results show that the growth morphology of Mg2（OH）2CO33H2O whisker is consistent with the model...From the perspective of growth units, the growth mechanism of Mg2（OH）2CO3.3H2O whisker is investigated in this paper. Results show that the growth morphology of Mg2（OH）2CO33H2O whisker is consistent with the model of anion coordination polyhedron growth units. The growth solution Raman shift of Mg2（OH）2CO;3H2O was monitored using Raman spectroscopy. The growth units are [Mg-（OH）4]2- and H2COv The growth process of Mg2（OH）2COf3H2O whisker is as follows： growth unit [Mg-（OH）4]2- first incorporates into the larger dimension [Mg-（OH）4]2-, then the [Mg-（OH）4]2-n combines with H2CO3 into a linear skeleton Mg2（OH）2CO3 in the same line. Mg2（OH）2CO3 combines with H2O by hydrogen bonds and ultimately transforms into Mg2（OH）2COf3H2O whisker. Magnesium carbonate whiskers have a layered structure, each of which is made of magnesium, carbon, oxygen, with H2O in between each layer. When skeletons are superimposed within the same plane as a parallelepiped one, they grow into solid cuboid-shaped whiskers. When the parallelepiped skeletons planes combine with each other through the cascading links, they grow into hollow cylindrical whiskers.展开更多
文摘目的探讨H3.3G34W、p63及SATB2在骨巨细胞瘤(giant cell tumor of bone,GCTB)中的表达情况及其联合应用对GCTB的诊断作用和价值。方法收集西安交通大学附属红会医院病理科2020年至2022年诊断的54例GCTB、83例非骨巨细胞瘤(non-giant cell tumor of bone,NGCTB)(包含14例动脉瘤样骨囊肿、16例软骨母细胞瘤和53例非骨化性纤维瘤)患者的样本和病历资料,采用免疫组织化学EliVision法检测H3.3G34W、p63及SATB2的表达情况。通过χ^(2)检验判断H3.3G34W、p63及SATB2的阳性率在各组间是否存在统计学差异;通过Logistic回归分析建立包括H3.3G34W、p63及SATB2的联合诊断模型,通过受试者工作特征(ROC)曲线分析评价模型的诊断价值。结果H3.3G34W、p63及SATB2在GCTB组中阳性率分别为81.5%、90.7%、92.6%;在NGCTB组中阳性率分别为2.4%、28.9%、62.7%。与NGCTB组相比,GCTB组患者年龄显著较大[(41.222±14.849)vs.(16.566±9.439);P<0.001],女性比男性患病率更高(51.9%vs.48.1%,P<0.001)。与NGCTB组相比,GCTB组中H3.3G34W(81.5%vs.2.4%,P<0.001);p63(90.7%vs.28.9%,P<0.001)和SATB2(92.6%vs.62.7%,P<0.001)的阳性率更高。单因素Logistic回归分析构建单因素预测模型,同时行ROC曲线分析,表明年龄(AUC=92.9%,P<0.001)、性别(AUC=64.5%,P=0.004)、H3.3G34W阳性率(AUC=89.5%,P<0.001)、p63阳性率(AUC=80.9%,P<0.001)、SATB2阳性率(AUC=65.0%,P=0.003)是GCTB诊断的独立预测因素。进一步的多因素Logistic回归分析构建混合预测模型,并行ROC曲线分析,发现混合模型展现出比单因素模型更好的预测价值(AUC=98.4%,P<0.001)。结论H3.3G34W、p63及SATB2是有效诊断GCTB的分子标记物,且三者联合应用更能提高GCTB的诊断预测效能。
基金supported by the National Program on the Key Basic Research Project of China(Nos.2017YFE0108200,2018YFA0108700,2016YFA0502302 and 2016YFA0500700)by NSFC(Nos.21807105,91753119,21977110,31571318,21778065 and 31771450)+1 种基金by the Strategic Priority Research Program,CAS(No.XDB 20000000)by Center for Excellence in Molecular Synthesis,CAS(No.FZHCZY020600)。
文摘Histone point mutations,including missense mutations on histone H3 at positions 27(K27M),34(G34R/V,G34W,G34L)and 36(K36M),were identified as potential cancer driver mutations.H3.3G34R/V mutations account for pediatric glioblastomas(GBM).RACK7(also known as ZMYND8,PRKCBP1)was recently reported to specifically bind H3.3G34R through its PHD(plant homedomain)domain(PHDRACK7)in vitro and in H3.3G34R pediatric glioblastoma cells,playing key roles in H3.3G34R-mediated gene transcription.Herein,we provided both biochemical and NMR structural evidences that PHDRACK7 recognized histone H3.3G34R mutant via a mechanism distinet from all other reported PHD domains.Except the reported residue D104,two new sites D108 and L121 of PHD^(RACK7) were found necessary for the interactions between PHD^(RACK7) and histone H3.3G34R peptide.Our results provided a potential molecular basis for pediatric GBM driven by the H3.3G34R mutation.
基金supported by the National Natural Science Foundation of China(91219202)to Guohong Li.the Ministry of Science and Technology of China(2015CB856200+2 种基金2011CB966300)the Chinese Academy of Sciences(CAS)Strategic Priority Research Program(XDA01010304)the National Natural Science Foundation of China(31301047)to Chaoyang Xiong
文摘Histones are the main protein components of eukaryotic chromatin. Histone variants and histone modifications modulate chromatin structure, ensuring the precise operation of cellular processes associated with genomic DNA. H3.3, an ancient and conserved H3 variant, differs from its canonical H3 counterpart by only five amino acids, yet it plays essential and specific roles in gene transcription, DNA repair and in maintaining genome integrity. Here, we review the most recent insights into the functions of histone H3.3, and the involvement of its mutant forms in human diseases.
文摘骨巨细胞瘤 (giant cell tumor of bone,GCTB)是发生在骨关节骺端的一种常见的交界性肿瘤,具有局部复发性以及罕见远处转移可能,很少发生恶性变。骨巨细胞瘤中的恶性肿瘤 (malignancy in giant cell tumor of bone,MGCTB),也就是过去称谓的恶性骨巨细胞瘤,在骨巨细胞瘤中含有高级别肉瘤成分。依据最初诊断时就证实同时存在高级别肉瘤成分.
基金Funded by the National Natural Science Foundation of China(No.51272207)
文摘From the perspective of growth units, the growth mechanism of Mg2（OH）2CO3.3H2O whisker is investigated in this paper. Results show that the growth morphology of Mg2（OH）2CO33H2O whisker is consistent with the model of anion coordination polyhedron growth units. The growth solution Raman shift of Mg2（OH）2CO;3H2O was monitored using Raman spectroscopy. The growth units are [Mg-（OH）4]2- and H2COv The growth process of Mg2（OH）2COf3H2O whisker is as follows： growth unit [Mg-（OH）4]2- first incorporates into the larger dimension [Mg-（OH）4]2-, then the [Mg-（OH）4]2-n combines with H2CO3 into a linear skeleton Mg2（OH）2CO3 in the same line. Mg2（OH）2CO3 combines with H2O by hydrogen bonds and ultimately transforms into Mg2（OH）2COf3H2O whisker. Magnesium carbonate whiskers have a layered structure, each of which is made of magnesium, carbon, oxygen, with H2O in between each layer. When skeletons are superimposed within the same plane as a parallelepiped one, they grow into solid cuboid-shaped whiskers. When the parallelepiped skeletons planes combine with each other through the cascading links, they grow into hollow cylindrical whiskers.
