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Related Concept Videos

Cancers Originate from Somatic Mutations in a Single Cell02:21

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Updated: Aug 6, 2025

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
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Multiple Mutations within Individual Oncogenes: Examples and Clinical Implications.

Keisuke Kataoka1,2, Yuki Saito2,3

  • 1Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

The Keio Journal of Medicine
|March 22, 2023
PubMed
Summary
This summary is machine-generated.

Multiple mutations (MMs) in oncogenes, not just single mutations, are common in cancer. These MMs, often on the same gene allele, have unique patterns and enhance cancer-driving activity.

Keywords:
EGFRNOTCH1PIK3CAmultiple mutationsoncogene

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Area of Science:

  • Oncology
  • Cancer Genomics
  • Molecular Biology

Background:

  • Traditionally, oncogenic mutations were viewed as single events.
  • Secondary mutations, like EGFR T790M, arise during treatment resistance.
  • Recent findings indicate multiple mutations (MMs) frequently occur in the same oncogene prior to therapy.

Approach:

  • Conducted a pan-cancer study to identify oncogenes affected by MMs.
  • Analyzed mutation type, position, and amino acid substitution patterns of MMs.
  • Investigated the co-occurrence of MMs on the same oncogene allele (cis-presentation).

Key Points:

  • Identified 14 pan-cancer and 6 cancer-specific oncogenes frequently impacted by MMs.
  • Observed that 9% of cases with mutations harbor MMs cis-presenting on the same allele.
  • MMs exhibit distinct mutational patterns compared to single mutations, overrepresenting weaker mutations that combine for enhanced oncogenic activity.

Conclusions:

  • Multiple mutations in oncogenes are a significant factor in human cancers.
  • MMs possess unique characteristics and mechanisms that contribute to oncogenesis.
  • Understanding MMs offers new insights into cancer mechanisms and potential clinical implications.