Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Lung Cancer. 2014 Mar;15(2):124-30. doi: 10.1016/j.cllc.2013.08.003. Epub 2013 Oct 26.

Mutation of TP53 and alteration of p14(arf) expression in EGFR- and KRAS-mutated lung adenocarcinomas.

Author information

  • 1International Agency for Research on Cancer, Lyon, France; Department of Thoracic Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Thoracic Oncology Department, Lille University Hospital, Université Lille Nord de France, Lille, France. Electronic address: alexis.cortot@chru-lille.fr.
  • 2International Agency for Research on Cancer, Lyon, France; Clinical Research Unit and Department of Pharmacology, Saint-Antoine University of Medicine, University Pierre et Marie Curie Paris 6, Paris, France.
  • 3International Agency for Research on Cancer, Lyon, France.
  • 4Department of Thoracic Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
  • 5Department of Pathology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
  • 6Department of Translational Research, Institut Gustave Roussy, Villejuif, France; INSERM Unit 981, University Paris-South, France.
  • 7Thorax Department, Institut Mutualiste Montsouris, Paris, France.
  • 8Department of Pathology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Department of Pathology, Institut Gustave Roussy, Villejuif, France.
  • 9Institut Albert Bonniot, INSERM U823 and Department of Pathology, Hôpital Albert Michallon, Grenoble, France.
  • 10International Agency for Research on Cancer, Lyon, France; International Prevention Research Institute, Lyon, France.

Abstract

BACKGROUND:

In lung adenocarcinoma, inactivation of the tumor suppressor p53 may abrogate a safeguard mechanism preventing the development of tumors with activating mutations in EGFR or KRAS. To assess this hypothesis, we analyzed TP53 mutations and downregulation of p14(arf), a negative regulator of p53 activated by oncogenic signals, in a retrospective series of 96 patients with primary adenocarcinoma of the lung.

PATIENTS AND METHODS:

Mutations in TP53 (exons 4-9), KRAS (exon 1), and EGFR (exons 18-21) were identified by direct sequencing of DNA from formalin-fixed, paraffin-embedded resected tumors. Expression of p14(arf) was semiquantitatively evaluated by immunohistochemical analysis.

RESULTS:

TP53, KRAS, and EGFR mutations were detected in 42 of 93 (45.2%), 15 of 95 (15.8%), and 31 of 90 (34.4%) cases, respectively. Low p14(arf) expression was observed in 19 of 91 cases (20.9%). Disruption of the p53/p14(arf) pathway (defined as TP53 mutation or decreased p14(arf) expression, or both) was observed in 18 of 31 EGFR-mutated (58.1%) tumors and in 9 of 13 KRAS-mutated (69.2%) tumors.

CONCLUSION:

Inactivation of the p53/p14(arf) pathway is common but not systematic in EGFR- or KRAS-mutated lung adenocarcinomas. Our work highlights the need to better investigate the association between EGFR and KRAS mutations and alterations in tumor suppressor pathways.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

EGFR; KRAS; Lung adenocarcinoma; p14(arf); p53

PMID:
24169260
[PubMed - in process]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk