Pan-cancer genetic profiles of mitotic DNA integrity checkpoint protein kinases

Ayana Meegol Rasteh1,2, Hengrui Liu3,4, Panpan Wang1

  • 1Cancer Research Institute, Jinan University, Guangzhou, China.

Insights

Protein kinases in the DNA integrity checkpoint pathway are implicated in cancer. This study profiles these kinases across 33 cancer types, revealing potential diagnostic and prognostic biomarkers for cancer therapy.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • The mitotic DNA integrity checkpoint signaling pathway is crucial for maintaining genomic stability.
  • Protein kinases play a central role in this pathway, with 16 key genes identified.
  • Dysregulation of this pathway is potentially linked to cancer development.

Purpose of the Study:

  • To generate pan-cancer profiles of 16 protein kinase genes involved in mitotic DNA integrity checkpoint signaling.
  • To investigate their potential as prognostic and diagnostic biomarkers.
  • To identify potential therapeutic targets for cancer treatment.

Main Methods:

  • Acquisition of multi-omic data for 16 protein kinase genes.
  • Analysis of over 9000 samples across 33 cancer types.
  • Profiling of single nucleotide variants (SNV), copy number variations (CNV), methylation, mRNA expression, pathway crosstalk, and microRNA regulation.

Main Results:

  • High SNV mutation frequencies observed in genes like ATM, PRKDC, and PLK1 in specific cancers (e.g., UCEC, SKCM).
  • CNVs of certain genes correlate with patient survival in UCEC, KIRP, and LGG.
  • mRNA expression of these genes may impact BRCA, KIRC, LUAD, and STAD, involving copy number, methylation, and miRNA regulation.

Conclusions:

  • Protein kinases in mitotic DNA integrity checkpoint signaling are implicated in cancer development.
  • These genes show potential as cancer diagnostic and prognostic biomarkers.
  • Further research is needed to validate clinical utility and develop therapeutic applications.

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.3K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.1K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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...
7.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K