低幅度的复制数增长通过已知和新瘤基因,以及相关的治疗脆弱性来塑造癌症
Thomas F Eleveld1, Bauke Ylstra2, Leendert H J Looijenga1,3
1Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.
Nucleic acids research
|July 22, 2025
概括
癌症中大量染色体复制数的增加是由瘤基因驱动的. 分析这些收益揭示了新的癌症驱动基因,并将它们与药物敏感性联系起来,推进精确瘤学.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 精确瘤学 精确瘤学
背景情况:
- 大量的染色体复制数在癌症中很常见,但驱动其优势的特定基因尚未得到充分理解.
- 这限制了它们在诊断和治疗策略中的临床用处.
研究的目的:
- 为了确定调解癌症复制数增长的选择性优势的基因.
- 探索拷贝数增加,瘤基因和药物敏感性/耐药性之间的关系.
- 评估副本数量的增长作为临床生物标志物的潜力.
主要方法:
- 分析胰腺癌数据集的复制数模式.
- 利用CRISPR查数据来识别介导基因.
- 与药物敏感性和耐药性数据相关联的副本数增加.
主要成果:
- 副本数量的增加主要是由已知的瘤基因驱动的.
- 确定了101个基因调解复制数增益效应,包括新的癌症相关基因.
- 发现了特定拷贝数增加和药物敏感性之间的关联,特别是对于瘤基因抑制剂.
结论:
- 大量的副本增加通过已知和新瘤基因都能获得选择性优势.
- 对副本数增加的系统分析可以识别潜在的治疗点和生物标志物.
- 这种方法对推进精确瘤学的前景充满希望.
相关概念视频
Cancer-Critical Genes I: Proto-oncogenes
9.2K
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...
9.2K
Cancers Originate from Somatic Mutations in a Single Cell
12.9K
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...
12.9K
Cancer-Critical Genes II: Tumor Suppressor Genes
8.1K
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...
8.1K
Adaptive Mechanisms in Cancer Cells
5.9K
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,...
5.9K
Comparing Copy Number Variations and SNPs
17.9K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
17.9K
Cancer
49.6K
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.
49.6K


