核毛孔复合体分解途径中的单核酸变异与骨髓瘤的生存率差相关
James E Jacobs1, Lara Davis1, Shannon McWeeney1
1Oregon Health & Science University, Portland, OR, United States.
Frontiers in genetics
|April 2, 2024
概括
核毛孔复合分解 (NPCD) 途径的异常与骨髓瘤的低生存率相关,独立于MYC过度表达. 这一发现为攻击性骨髓瘤和潜在的治疗点提供了新的见解.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 骨髓瘤是一种具有挑战性的骨癌,特别是在转移性疾病的年轻患者中.
- 开发向疗法受到缺乏一致的遗传标记物的阻碍.
- MYC过度表达与不良结果有关,但需要其他预后标志物.
研究的目的:
- 确定与骨髓瘤整体存活率相关的基因组特征.
- 定义与侵袭性疾病相关的异常分子通路签名.
- 探索在骨髓瘤中超越MYC的新型遗传驱动因素.
主要方法:
- 106个骨髓瘤瘤的全基因组测序和匹配的对照.
- 单核酸变体和差异性基因表达的分析.
- 路径丰富分析侧重于核毛孔复合体分解 (NPCD) 和MYC响应基因.
主要成果:
- 在NPCD途径中的突变与较差的整体存活率有显著的相关性.
- 免疫反应和调节基因在NPCD异常瘤中得到丰富.
- 无论是MYC还是MYC响应基因,在NPCD异常和非异常组之间都没有显示差异性表达.
- NPCD路径突变主要是调节变异,表明表观遗传失调.
结论:
- NPCD路径异常代表了一种新的,MYC独立的标志物,用于骨髓瘤的不良预后.
- 这些发现强调了基因调节网络失调在侵袭性骨髓瘤中的作用.
- 识别NPCD路径异常可能会导致新的个性化治疗策略.
相关概念视频
The Nucleolus
8.8K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.8K
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
Long-patch Base Excision Repair
7.0K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
Loss of Tumor Suppressor Gene Functions
4.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.8K
Nucleosome Remodeling
9.1K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.1K


