SFyNCS检测了癌症的非编码序列的瘤融合
Xiaoming Zhong1, Jingyun Luan1, Anqi Yu1
1Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Nucleic acids research
|August 28, 2023
概括
科学家们开发了SFyNCS,这是一种检测致癌的融合基因的工具,包括那些涉及非编码序列的基因. 这种新方法显著提高了检测准确度,揭示了瘤中广泛存在的非编码融合.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 生物信息学是一种生物信息学.
背景情况:
- 融合基因是癌症的确立驱动因素,但大多数已识别的致癌融合涉及蛋白质编码基因.
- 由于缺乏有效的工具,检测涉及非编码序列的融合一直受到限制.
研究的目的:
- 开发和验证SFyNCS,这是一种用于从转录基因数据中检测蛋白质编码和非编码融合序列的新型工具.
- 综合评估融合检测策略,使用基因组结构变异数据进行验证.
主要方法:
- 在转录基因数据中开发SFyNCS用于核聚变检测.
- 从基因组测序中整合体质结构变异数据,用于融合验证.
- 使用癌症细胞系和患者样本对现有算法进行SFyNCS的广泛比较.
- 在癌症基因组图谱 (TCGA) 队列中应用SFyNCS (9565个瘤样本,33种瘤类型).
主要成果:
- 与当前的核聚变检测算法相比,SFyNCS显示出更高的灵敏度和特异性.
- 对9565个TCGA样本的分析揭示了165139个融合,其中72%涉及非编码序列.
- 长非编码RNA与瘤基因的反复融合在前列腺癌的3%中被发现.
- 在32%的无差异化脂类瘤中发现了两个非编码RNA之间的融合,在小鼠模型中验证了瘤功能.
结论:
- SFyNCS显著提升了融合基因的检测,特别是那些涉及非编码序列的基因.
- 非编码融合在癌症中很普遍,并且代表了以前被低估的大量瘤原因驱动因素.
- 这些发现为癌症诊断和针对非编码融合的治疗策略开辟了新的途径.
相关概念视频
Cancers Originate from Somatic Mutations in a Single Cell
12.0K
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...
12.0K
Cancer-Critical Genes I: Proto-oncogenes
9.0K
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...
9.0K
Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
Rous Sarcoma Virus (RSV) and Cancer
5.1K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
5.1K
Tagging and Fusion Proteins
6.7K
Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
6.7K
Induced Pluripotent Stem Cells
4.2K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.2K


