癌症相关的生殖线风险变异的功能分析
Laura N Kellman1,2, Poornima H Neela1, Suhas Srinivasan1
1Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Nature genetics
|February 17, 2025
概括
调节性DNA中的遗传变异会影响遗传的癌症风险. 这项研究确定了特定的SNV (单核酸变异) 和它们的基因,揭示了它们如何激活促进癌症的途径.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子遗传学 分子遗传学
背景情况:
- 在非编码DNA区域的单核酸变体 (SNV) 越来越多地被认为是导致遗传癌症风险的因素.
- 了解这些SNV的功能影响对于识别高风险个体和制定有针对性的干预措施至关重要.
研究的目的:
- 为了功能性地描述与13种主要人类癌症相关的数千种SNV.
- 通过改变调节性DNA功能来识别特定的SNV及其向基因,这些基因通过改变调节性DNA功能来促进癌症风险.
- 探索这些风险相关的SNV所涉及的分子途径.
主要方法:
- 大规模并行报告测试 (MPRAs) 用于测试4041种与癌症相关的SNVs在相关的人类细胞类型中的调节活性.
- 将MPRA数据与表观遗传学 (染色体可访问性,DNA循环) 和遗传学 (表达量化特征位点) 数据集集成.
- 使用CRISPR-Cas9淘汰屏幕来评估候选风险基因在癌细胞生长中的作用.
- 特定SNV (rs10411210) 的功能编辑,以确定其对基因表达和通路激活的影响.
主要成果:
- 380个潜在的调节性SNV及其假定的基因被提名.
- 这些SNV涉及到癌症风险中的关键细胞过程,包括线粒体翻译,DNA损伤修复和Rho GTPase信号传递.
- 鉴定出的生殖危险基因的一个子集也支持了已确定的癌症的生长.
- 编辑rs10411210表明其风险等位基因增强RHPN2表达和RhoA激活,将单个SNV与促进癌症的途径联系起来.
结论:
- 这项研究提供了功能验证的,与癌症相关的调节性SNV及其向基因的宝贵资源.
- 这些发现突出了通过遗传遗传变异可以增加终身癌症风险的特定分子通路.
- 这些数据可以为遗传风险评估提供变异优先级信息,并指导对癌症倾向的机制研究.
相关概念视频
Cancer-Critical Genes II: Tumor Suppressor Genes
7.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.3K
Cancers Originate from Somatic Mutations in a Single Cell
11.4K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.4K
Cancer-Critical Genes I: Proto-oncogenes
8.7K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.7K
Cancer Survival Analysis
321
Cancer survival analysis focuses on quantifying and interpreting the time from a key starting point, such as diagnosis or the initiation of treatment, to a specific endpoint, such as remission or death. This analysis provides critical insights into treatment effectiveness and factors that influence patient outcomes, helping to shape clinical decisions and guide prognostic evaluations. A cornerstone of oncology research, survival analysis tackles the challenges of skewed, non-normally...
321
Cancer Prevention
6.0K
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
6.0K
Loss of Tumor Suppressor Gene Functions
4.7K
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...
4.7K


