Low frequency of EGFR mutations in pleural mesothelioma patients, Cologne, Germany

Our plain-English summary of Low frequency of EGFR mutations in pleural mesothelioma patients, Cologne, Germany, by V. Schildgen, O. Pabst, R.L. Tillmann, et al (Applied Immunohistochemistry & Molecular Morphology, 2015).

The study

• Authors: V. Schildgen, O. Pabst, R.L. Tillmann, J. Lüsebrink, O. Schildgen, C. Ludwig, M. Brockmann, E. Stoelben
• Journal: Applied Immunohistochemistry & Molecular Morphology
• Published: 2015;23(2):118-25
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

EGFR mutations were previously found in patients suffering from peritoneal mesothelioma but have not yet been described in pleural mesothelioma. The aim of the present study was the identification of EGFR mutations in patients suffering from pleural mesothelioma. Pleural mesothelioma tissue from 31 patients was used to analyze possible mutations in the EGFR gene comprising the exons 18-21 with the codons 719, 768, 790, 858+861, 731+734, 785, 797+801, 831, and 868 with pyrosequencing. The results indicate that 31 pleural mesothelioma patients show a wild-type EGFR gene when analyzing the codons D19, 768, 790, 858+861, 731+734, 785, 797+801, 831, and 868, whereas 2 patients have a mutation in the EGFR gene in codon 719. Sanger sequencing of the EGFR codon 785 was used for the determination of a polymorphism in the sequencing of tumor-free patients and pleural mesothelioma patients with a distribution of a wild-type homozygous sequence with guanine, a wild-type heterozygous sequence having guanine and adenine, a wild-type homozygous sequence with adenine, and a wild-type heterozygous sequence with adenine and guanine. Next, the identification of less EGFR mutations in the EGFR gene of the pleural mesothelioma an up to this time unknown polymorphism in the EGFR gene was identified which could be wrongly interpreted as a mutation.

In plain English

This laboratory study from a Cologne, Germany hospital looked for mutations in a gene called EGFR in stored tumor tissue from 31 patients with pleural mesothelioma. The authors said the disease was induced "most likely" by mineral fibers. Their introduction named asbestos and erionite as causes of mesothelioma generally, but the study did not measure these patients' exposure. Tumor-free tissue from people examined for suspected tuberculosis served as controls. Two patients (13 and 26) had the same mutation, G719C, at codon 719. The article reported mutation frequencies of 4.3% and 7.2% in those two samples. No mutations were found at the other locations tested, including five more locations checked in 30 patients. None of the control samples had mutations. A few bases downstream of the codon 785 site, the authors found a natural guanine-or-adenine variation in both patients and controls. They described this as a previously unknown polymorphism that could be wrongly read as a mutation. The authors concluded that EGFR mutations were not observed outside the first set of locations tested, where the 2 mutations were found.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory genetic analysis of archived tumor tissue, using commercial and in-house pyrosequencing plus Sanger sequencing, with tumor-free control samples
• Who was studied: 31 patients with pleural mesothelioma treated at a hospital in Cologne, Germany, whose tissue had been archived during the past decade. Controls were 10 tumor-free samples from patients with suspected tuberculosis infection but no tumor; 9 of these were used for the in-house codons because one lacked enough DNA.
• Exposure: Not measured. The authors stated the pleural mesothelioma was induced most likely by exposure to mineral fibers. Their introduction named asbestos and erionite as causes of mesothelioma in general, but no fiber types, jobs or doses were given for these patients.
• Main results:
  • 2 of 31 pleural mesothelioma patients (patients 13 and 26) had a mutation at EGFR codon 719 in exon 18; the other 29 had the normal (wild-type) gene at that codon
  • Both mutations were the amino acid substitution G719C (cysteine instead of glycine)
  • The reported mutation frequency was 4.3% in patient 13 and 7.2% in patient 26
  • None of the 31 patients had a mutation in exon 19, at codons 768 and 790 in exon 20, or at codons 858-861 in exon 21
  • No mutations were found at codons 731+734, 785, 797+801, 831 and 868 in the 30 pleural mesothelioma samples analyzed
  • All tumor-free control samples showed a wild-type EGFR gene at codons Del19, 719, 768, 790 and 858-861
  • The base variation was located downstream of the codon 785 hotspot, and codon 785 itself was wild type in all 30 pleural mesothelioma samples
  • In the codon 785 region, the 30 pleural mesothelioma samples plus 1 positive control DNA fell into four sequence patterns: guanine only 5 (16%), guanine and adenine 1 (3%), adenine and guanine 13 (42%), adenine only 12 (39%)
  • In the codon 785 region, the 9 tumor-free samples plus 1 positive control showed adenine and guanine in 7 (70%) and adenine only in 3 (30%)
  • The authors interpreted this variation as a previously unknown polymorphism that could be mistaken for a mutation
• The authors' conclusion: The authors concluded that EGFR mutations in pleural mesothelioma were not observed outside codons Del19, 719, 768, 790 and 858+861, where 2 mutations were found. They also recommended analyzing other regions of the EGFR gene.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: EGFR, Pleural Mesothelioma, Peritoneal Mesothelioma.

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