用SPRINTER鉴定单细胞克隆中癌症扩散的进化动态
Olivia Lucas1,2,3,4, Sophia Ward2,3,5, Rija Zaidi1,2
1Computational Cancer Genomics Research Group, University College London Cancer Institute, London, UK.
Nature genetics
|November 29, 2024
概括
癌症克隆表现出不同的增殖率,影响转移. SPRINTER算法分析单细胞测序数据以揭示这种异质性,识别具有更大的转移潜力和改变基因表达的高增殖克隆.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 计算生物学 计算生物学
背景情况:
- 癌症扩散是恶性瘤的标志,但克隆间的差异仍然不太清楚.
- 瘤有进化上不同的克隆,可能具有不同的生物行为.
研究的目的:
- 开发和验证一个计算算法,SPRINTER,用于推断跨瘤克隆的单细胞增殖率.
- 调查非小细胞肺癌 (NSCLC) 和其他癌症中克隆特异的扩散异质性.
主要方法:
- 通过进化路径 (SPRINTER) 算法开发了非同质瘤的单细胞增殖率推断.
- 利用来自NSCLC,乳腺和卵巢癌数据集的单细胞全基因组DNA测序数据.
- 为准确的S和G2阶段细胞识别和克隆分配生成了基础真实数据.
主要成果:
- SPRINTER揭示了NSCLC中显著的克隆增殖异质性,得到了正交实验数据的支持.
- 高增殖克隆表明转移性播种潜力增加和循环瘤DNA流失.
- 观察到与繁殖和转移相关的基因复制时间的克隆特异性变化.
- 对乳腺和卵巢癌数据的分析显示,高增殖克隆的单细胞基因组变异率增加和基因放大.
结论:
- 克隆特异性增殖率是瘤生物学中一个关键的,以前未被描述的方面.
- 斯普林特为剖析瘤异质性及其临床影响提供了一个强大的工具.
- 了解克隆之间的增殖差异可以为癌症进展和治疗策略提供信息.
相关概念视频
Cancers Originate from Somatic Mutations in a Single Cell
11.6K
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...
11.6K
Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K
Cancer
48.0K
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
48.0K
Cancer Stem Cells and Tumor Maintenance
4.9K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.9K
Replicative Cell Senescence
3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Tumor Progression
6.2K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K


