Patients with peritoneal mesothelioma lack epidermal growth factor receptor tyrosine kinase mutations that would make them sensitive to tyrosine kinase inhibitors

The epidermal growth factor receptor (EGFR) is a promising target for cancer therapy. The presence of certain somatic mutations in the tyrosine kinase (TK) domain of the EGFR gene is associated with clinical response to TK inhibitors (TKI) in patients with lung adenocarcinoma. In this study we evaluated the status of somatic mutations in the entire TK domain of the EGFR gene by direct sequencing using early passage peritoneal mesothelioma cells, established cell lines as well as 33 peritoneal mesothelioma tumor samples. No novel mutations were found in the cell lines. Sequence analysis of the EGFR TK domain revealed the presence of a silent polymorphism (c.2607G→A, Q787Q) at exon 20 of both peritoneal mesothelioma cell lines as well as tumor specimens. The frequency of genotypes AA and GA was 42.8 and 57.2% in the cell lines and 33.3 and 57.6% in tumor specimens, respectively. The TKI erlotinib showed an IC50 in the range of 10-50 µM in five out of the seven cell lines with a GA genotype while all five cell lines with the AA genotype had an IC50 >50 µM. Of the 33 peritoneal mesothelioma tumor samples analyzed none had an EGFR TKI sensitizing mutation and only one specimen showed an earlier reported somatic mutation at codon 850 in exon 21 of the EGFR gene. Our data show that patients with peritoneal mesothelioma do not harbor somatic mutations in the EGFR TK domain that would make them sensitive to EGFR TKI.