Related Experiment Video

Updated: Aug 8, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Absence of R24C mutation of the CDK4 gene in leukemias and solid tumors

Naoki Mori1, Rong Yang, Norihiko Kawamata

  • 1Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA. mori@dh.twmu.ac.jp

International Journal of Hematology
|May 7, 2003
PubMed

Insights

The R24C mutation in the cyclin-dependent kinase 4 (CDK4) gene, linked to melanoma, was not found in most other human cancers. This suggests CDK4 mutations are rare in neoplasms due to functional loss.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The R24C mutation in the cyclin-dependent kinase 4 (CDK4) gene affects p16(INK4a) binding.
  • This mutation has been observed in some melanoma cases.

Purpose of the Study:

  • To investigate the prevalence of the CDK4 R24C mutation in various human tumors.
  • To understand why CDK4 mutations might be rare in non-melanoma cancers.

Main Methods:

  • Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of 273 tumors and 49 cell lines.
  • Yeast two-hybrid screening of randomly mutagenized CDK4.
  • Sequence analysis and in vitro kinase assays.

Main Results:

  • No CDK4 R24C mutations were detected in the analyzed leukemias and solid tumors.
  • Most randomly generated CDK4 mutations disrupting p16(INK4a) binding also abolished CDK4 kinase activity.

Conclusions:

  • The CDK4 R24C mutation is rare in most human neoplasms, unlike in melanoma.
  • The loss of CDK4 activity associated with p16(INK4a) binding disruption likely explains the rarity of these mutations in cancer.

More Related Videos

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Related Concept Videos

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.
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...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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 daughter...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...