Related Experiment Video

Updated: Jul 6, 2025

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
09:49

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

Published on: July 5, 2019

9.6K

Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer

Yi Bei1, Luca Bramé1,2, Marieluise Kirchner3

  • 1Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Cancer Discovery
|January 10, 2024
PubMed

Insights

Passenger gene coamplifications in cancer can create new therapeutic vulnerabilities. The DEAD-Box Helicase 1 (DDX1) gene coamplification increases reliance on the mTOR pathway, offering a new target for cancer therapy.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • DNA amplifications in cancer frequently harbor oncogenes.
  • Passenger coamplifications, often overlooked, may also influence cancer progression and treatment.
  • Understanding these passenger events is crucial for comprehensive cancer therapy strategies.

Purpose of the Study:

  • To investigate if passenger gene coamplifications create collateral therapeutic vulnerabilities.
  • To identify specific dependencies arising from passenger coamplifications.
  • To explore the therapeutic potential of targeting vulnerabilities created by passenger genes.

Main Methods:

  • Analysis of over 3,000 cancer genomes.
  • Interrogation of CRISPR-Cas9 loss-of-function screens in over 700 cancer cell lines.
  • Proof-of-principle study involving the DEAD-Box Helicase 1 (DDX1) gene, interaction proteomics, and live-cell metabolomics.

Main Results:

  • Passenger coamplifications are associated with distinct cancer cell dependency profiles.
  • Coamplification of the passenger gene DDX1 enhances dependency on the mTOR pathway.
  • DDX1 interacts with tricarboxylic acid (TCA) cycle components, impairing TCA activity and increasing mTORC1 activity.
  • Disruption of mTORC1 leads to significant cancer cell death in vitro and in vivo.

Conclusions:

  • Structurally linked coamplification of passenger genes and oncogenes can lead to collateral therapeutic vulnerabilities.
  • Passenger coamplifications represent a significant, previously underappreciated source of cancer dependencies.
  • This principle offers a promising avenue for expanding target discovery in oncology.

More Related Videos

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes08:32

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

Published on: May 23, 2025

185
Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis09:45

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

Published on: March 31, 2015

11.2K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
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...
7.4K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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...
8.9K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.6K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

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...
11.9K