基因组进化和转录变化,使前列腺癌演变为神经内分泌和导管癌类型
Srinivasa R Rao1, Andrew Protheroe1, Lucia Cerundolo1
1Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK.
International journal of molecular sciences
|August 26, 2023
概括
神经内分泌前列腺癌,通常是侵略性的,可以与管道腺癌有共同的起源. 整个基因组的翻倍与前列腺癌复发和不良预后有关.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 基因组学就是基因组学.
背景情况:
- 前列腺癌通常呈现为acinar腺癌,但可以表现为具有侵略性的神经内分泌或导管类型.
- 神经内分泌前列腺癌通常在雄激素剥夺疗法或de novo期间出现.
- 了解这些多样化的前列腺癌亚型的起源对于有效治疗至关重要.
研究的目的:
- 调查神经内分泌和导管前列腺癌的潜在共同祖先.
- 为了确定与侵袭性前列腺癌亚型和复发相关的基因组变化.
主要方法:
- 从两个病例的前列腺癌组织档案的外捕获测序.
- 在一个案例中,长度采样为5年.
- 遗传学分析以确定瘤的进化和祖先.
主要成果:
- 在案例1中证明了小细胞神经内分泌和导管性前列腺癌之间的共同祖先.
- 在案例1的所有样本中确定了全基因组翻倍,这表明它在前列腺癌复发中的作用.
- 在案例2中观察到明显的基因组变化,包括13q损失 (RB1) 和17p损失 (TP53),与与治疗相关的神经内分泌前列腺癌相关.
结论:
- 提供了小细胞神经内分泌和导管性前列腺癌之间共同起源的第一个证据.
- 突出了整个基因组的翻倍,作为复发性前列腺癌预后不佳的重要指标.
相关概念视频
Tumor Progression
6.4K
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...
6.4K
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
Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
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
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
Exon Recombination
3.6K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K


