遗传背景和瘤驱动因素决定了乳腺瘤转移的基因组进化和转录组学
Christina R Ross1,2, Karol Szczepanek1,3, Jack Sanford1,4
1Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Communications biology
|August 14, 2025
概括
致癌驱动因素和遗传背景显著影响癌症转移. 这项研究揭示了这些因素如何塑造不同乳腺癌亚型的转移性病变中的基因组和基因表达变化.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
背景情况:
- 转移是癌症死亡率的主要驱动因素.
- 之前在MMTV-PyMT模型中的研究提供了基本的见解.
- 了解转移的基因组和转录基础是至关重要的.
研究的目的:
- 调查瘤驱动因素和遗传背景对转移的影响.
- 分析体位点突变,拷贝数变异和转移性病变中的基因表达.
- 探索这些变化如何汇聚到关键的细胞过程中.
主要方法:
- 利用了四种不同的小鼠模型,代表了光线性,HER2增强型和三阴性乳腺癌亚型.
- 进行了转录组分析,以评估转移特异性基因表达 (MSGE).
- 分析了转移特异性拷贝数变异 (MSCNVs) 和体点突变.
主要成果:
- 在模型中观察到有限的转移相关的体位点突变.
- 瘤性驱动因素显著影响MSCNV,而常见的驱动者独立的MSCNV很少见.
- 遗传背景对MSCNV产生了深远的影响,而瘤性驱动因素形成了独特的MSGE配置文件.
- 功能分析表明免疫反应,新陈代谢和细胞外矩阵相互作用的趋同.
结论:
- 致癌驱动因素和遗传背景是转移性景观的关键决定因素.
- 基因组变化 (MSCNVs) 和基因表达变化 (MSGE) 都会导致转移.
- 这些机制调节了对转移性进展至关重要的基本细胞过程.
更多相关视频
相关概念视频
Tumor Progression
6.5K
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...
6.5K
Metastasis
5.7K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.7K
Cancer-Critical Genes I: Proto-oncogenes
9.1K
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...
9.1K
Cancers Originate from Somatic Mutations in a Single Cell
12.7K
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...
12.7K
Mouse Models of Cancer Study
5.7K
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
5.7K
The Tumor Microenvironment
6.8K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.8K


