H3K27M突变的扩散性结质瘤的特征,其非中线位置
Souhir Guidara1, Antoine Seyve2, Delphine Poncet3,4
1Department of Medical Genetics, Hedi Chaker Hospital, Sfax, Tunisia. souhir.guidara89@gmail.com.
Journal of neuro-oncology
|June 27, 2024
概括
有H3K27M突变的扩散中线质瘤 (DMG) 是具有攻击性的. 具有H3K27M突变的罕见非中线性质瘤 (DNMG) 与DMG共享特征,表明类似的罕见表现和新疗法的潜在益处.
科学领域:
- 神经瘤学神经瘤学
- 分子病理学分子病理学
- 癌症基因组学 癌症基因组学
背景情况:
- 有H3K27M突变的扩散中线质瘤 (DMG) 是一种侵略性的脑瘤.
- 在扩散非中线质瘤 (DNMG) 中很少发现H3K27M突变.
- H3K27M突变DNMG的分类和特征仍然不清楚.
研究的目的:
- 分析具有H3K27M突变的DNMG的临床,放射和分子特征.
- 为了将H3K27M突变DNMG与其中线对应物进行比较.
- 确定这些罕见瘤的最佳分类和潜在的治疗策略.
主要方法:
- 对H3K27M突变扩散质瘤患者 (2016-2023) 的回顾性审查.
- 鉴定和分子表征 (DNA甲基化,测序) 的H3K27M突变DNMG.
- 对之前报告的H3K27M突变DNMG病例的文献综述.
主要成果:
- 在51个H3K27M突变扩散质瘤中发现了两个H3K27M突变DNMG病例.
- 总共审查了39例H3K27M突变DNMG病例,主要是在叶.
- 预后不佳 (平均整体存活时间为10.3个月),经常出现TP53,ATRX和PDGFRA变化.
- 分子分析显示H3K27M突变DNMG与H3K27M突变DMG聚集在一起,PDGFRA变化更频繁.
结论:
- H3K27M突变DNMG代表H3K27M突变DMG的一个罕见的解剖变体.
- 这些瘤与中线瘤有着分子和临床相似之处.
- H3K27M突变DNMG可能会对新的治疗方法做出反应,例如ONC201.1.
相关概念视频
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
02:39lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...