Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma

R. Mezzapelle, U. Miglio, O. Rena, A. Paganotti, S. Allegrini, J. Antona, F. Molinari, M. Frattini, G. Monga, O. Alabiso, R. Boldorini

Research output: Contribution to journalArticle

Abstract

Background: As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies.Methods:After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing.Results:Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552).Conclusions:Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials.

Original languageEnglish
Pages (from-to)1743-1749
Number of pages7
JournalBritish Journal of Cancer
Volume108
Issue number8
DOIs
Publication statusPublished - Apr 30 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Mezzapelle, R., Miglio, U., Rena, O., Paganotti, A., Allegrini, S., Antona, J., Molinari, F., Frattini, M., Monga, G., Alabiso, O., & Boldorini, R. (2013). Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma. British Journal of Cancer, 108(8), 1743-1749. https://doi.org/10.1038/bjc.2013.130