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Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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The Ras Gene02:38

The Ras Gene

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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...
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Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

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Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
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Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

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Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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The Retinoblastoma Gene01:20

The Retinoblastoma Gene

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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,...
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Author Spotlight: Advancing the Detection of Low-Frequency Mutations in Cancer Tissues
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RHOA mutations in peripheral T cell lymphoma.

Jan Cools1

  • 1VIB Center for the Biology of Disease and the KU Leuven Center for Human Genetics, Leuven, Belgium.

Nature Genetics
|March 29, 2014
PubMed
Summary

Peripheral T cell lymphomas, aggressive cancers of T lymphocytes and NK cells, are linked to a specific RHOA GTPase gene mutation. This dominant-negative mutation is a key finding in understanding these rare lymphomas.

Area of Science:

  • Oncology
  • Hematology
  • Molecular Biology

Background:

  • Peripheral T cell lymphomas (PTCLs) are aggressive hematologic malignancies.
  • These cancers originate from mature T lymphocytes or natural killer (NK) cells.
  • The genetic underpinnings of PTCLs remain incompletely understood.

Purpose of the Study:

  • To investigate the genetic landscape of peripheral T cell lymphomas.
  • To identify recurrent mutations contributing to lymphomagenesis.
  • To explore the role of specific genes in PTCL development.

Main Methods:

  • Genomic analysis of PTCL patient samples.
  • Identification and characterization of mutations in key signaling genes.
  • Functional studies to assess the impact of identified mutations.

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Main Results:

  • A recurrent dominant-negative mutation in the RHOA GTPase gene was identified.
  • This mutation was found to be prevalent in specific subtypes of PTCL.
  • The RHOA mutation likely plays a significant role in the pathogenesis of these lymphomas.

Conclusions:

  • The RHOA GTPase gene is a frequently mutated driver in peripheral T cell lymphomas.
  • Targeting RHOA signaling pathways may offer novel therapeutic strategies.
  • Understanding these mutations advances the molecular classification of PTCLs.