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Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin

Yoo Ri Kim1, Ji Eun Oh, Min Sung Kim

  • 1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

The Journal of Pathology
|December 8, 2009
PubMed

Insights

Nuclear factor erythroid-related factor 2 (NRF2) mutations are common in squamous cell carcinomas (SCCs) of the esophagus and skin. These NRF2 mutations promote cancer development and are a key feature of SCCs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Nuclear factor erythroid-related factor 2 (NRF2) is a transcription factor regulating cytoprotective proteins against oxidative stress.
  • Mutations in NRF2 that inactivate KEAP1-mediated degradation are implicated in lung and head/neck cancers.

Purpose of the Study:

  • To investigate the occurrence and significance of NRF2 mutations in a broader spectrum of human cancers.
  • To determine if NRF2 mutations are associated with specific cancer types, particularly squamous cell carcinomas (SCCs).

Main Methods:

  • Analysis of 1145 cancer tissues from various origins including carcinomas and hematological malignancies.
  • Single-strand conformation polymorphism (SSCP) assay was used to detect NRF2 mutations.
  • NRF2 protein expression was assessed in tumor nuclei.

Main Results:

  • NRF2 mutations were detected in esophageal (11.4%), skin (6.3%), lung (8.0%), and larynx (13.0%) cancers.
  • Over 95% of identified NRF2 mutations occurred in squamous cell carcinomas (SCCs).
  • Mutations were located near critical NRF2-KEAP1 interaction motifs, and affected SCCs showed increased nuclear NRF2 expression without KEAP1 mutations.

Conclusions:

  • NRF2 mutations are not limited to lung and head/neck cancers but are also prevalent in esophageal and skin cancers.
  • NRF2 mutations play a significant role in the development of SCC and are a characteristic feature of this cancer subtype.

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