Related Experiment Video

Updated: Feb 5, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

416

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer

A Kron1, C Alidousty2, M Scheffler1

  • 1Network Genomic Medicine, Cologne, Germany; Lung Cancer Group Cologne, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology Köln Bonn, Cologne, Germany.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|August 31, 2018
PubMed
Abstract

Insights

Co-occurring TP53 mutations in ALK-rearranged non-small-cell lung cancer (NSCLC) patients significantly reduce progression-free survival and overall survival, regardless of treatment. These findings highlight TP53 as a negative prognostic marker in ALK-rearranged NSCLC.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Systemic therapy outcomes in ALK-rearranged non-small-cell lung cancer (NSCLC) can be influenced by co-occurring mutations.
  • Investigating these co-mutations is crucial for understanding treatment efficacy.

Purpose of the Study:

  • To analyze the impact of co-occurring mutations on the efficacy of systemic therapy in patients with ALK-rearranged NSCLC.
  • To identify specific mutations that predict treatment outcomes.

Main Methods:

  • Retrospective analysis of 216 patients with ALK-rearranged NSCLC (stage IIIB/IV).
  • Utilized next-generation sequencing and fluorescence in situ hybridization for mutation analysis.
  • Determined median progression-free survival (PFS) and overall survival (OS) and performed Cox regression analyses.

Main Results:

  • TP53 mutations were present in 23.8% of ALK-rearranged NSCLC patients; other co-mutations were rare.
  • ALK/TP53 co-mutated patients had significantly lower median PFS (3.9 vs. 10.3 months) and OS (15.0 vs. 50.0 months) compared to TP53 wildtype patients.
  • This survival disadvantage was consistent across various treatment subgroups, including chemotherapy and ALK-inhibitor therapies.

Conclusions:

  • Co-occurring TP53 mutations are a significant negative predictor of systemic therapy outcomes in ALK-rearranged NSCLC.
  • Further research into the molecular mechanisms of ALK/TP53 co-mutated NSCLC is warranted to improve treatment strategies.

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

25.1K
Intraperitoneal Glucose Tolerance Test, Measurement of Lung Function, and Fixation of the Lung to Study the Impact of Obesity and Impaired Metabolism on Pulmonary Outcomes08:30

Intraperitoneal Glucose Tolerance Test, Measurement of Lung Function, and Fixation of the Lung to Study the Impact of Obesity and Impaired Metabolism on Pulmonary Outcomes

Published on: March 15, 2018

14.7K

Related Concept Videos

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...
14.9K
Mutations01:39

Mutations

Overview
94.5K
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...
3.8K
[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement01:21

[3,3] Sigmatropic Rearrangement of 1,5-Dienes: Cope Rearrangement

The Cope rearrangement is classified as a [3,3] sigmatropic shift in 1,5-dienes, leading to a more stable, isomeric 1,5-diene. The reaction involves a concerted movement of six electrons, four from two π bonds and two from a σ bond, via an energetically favorable chair-like transition state.
3.4K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.9K
[3,3] Sigmatropic Rearrangement of Allyl Vinyl Ethers: Claisen Rearrangement01:24

[3,3] Sigmatropic Rearrangement of Allyl Vinyl Ethers: Claisen Rearrangement

The Claisen rearrangement is a [3,3] sigmatropic rearrangement of allyl vinyl ethers to unsaturated carbonyl compounds. The rearrangement is a concerted pericyclic reaction proceeding via a chair-like transition state.
2.8K