Spectrum of EGFR gene copy number changes and KRAS gene mutation status in korean triple negative breast cancer patients

Yoonjung Kim, Juwon Kim, Hy De Lee, Joon Jeong, Woochang Lee, Kyung A. Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Anti-epidermal growth factor receptor (EGFR) therapy has been tried in triple negative breast cancer (TNBC) patients without evaluation of molecular and clinical predictors in several randomized clinical studies. Only fewer than 20% of metastatic TNBCs showed response to anti-EGFR therapy. In order to increase the overall response rate, first step would be to classify TNBC into good or poor responders according to oncogenic mutation profiles. This study provides the molecular characteristics of TNBCs including EGFR gene copy number changes and mutation status of EGFR and KRAS gene in Korean TNBC patients. Mutation analysis for EGFR, KRAS, BRAF and TP53 from a total of 105 TNBC tissue samples was performed by direct sequencing, peptide nucleic acid-mediated PCR clamping method and real-time PCR. Copy number changes of EGFR gene were evaluated using multiplex ligation-dependent probe amplification. Out of all 105 TNBCs, 15.2% (16/105) showed EGFR copy number changes. Among them, increased or decreased EGFR copy number was detected in 13 (5 single copy gain, 2 amplification and 4 high-copy number amplification) and 3 cases (3 hemizygous deletion), respectively. The mutation frequencies of KRAS, EGFR and TP53 gene were 1.9% (G12V and G12D), 1.0% (exon 19 del) and 31.4%, respectively. There was no BRAF V600E mutation found. Future studies are needed to evaluate the clinical outcomes of TNBC patients who undergo anti-EGFR therapy according to the genetic status of EGFR.

Original languageEnglish
Article numbere79014
JournalPloS one
Volume8
Issue number10
DOIs
Publication statusPublished - 2013 Oct 30

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Triple Negative Breast Neoplasms
erbB-1 Genes
gene dosage
Gene Dosage
Epidermal Growth Factor Receptor
breast neoplasms
Genes
mutation
Mutation
genes
Amplification
Peptide Nucleic Acids
therapeutics
Multiplex Polymerase Chain Reaction
p53 Genes
Mutation Rate
epidermal growth factor receptors
Constriction
Real-Time Polymerase Chain Reaction
Exons

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "Spectrum of EGFR gene copy number changes and KRAS gene mutation status in korean triple negative breast cancer patients",
abstract = "Anti-epidermal growth factor receptor (EGFR) therapy has been tried in triple negative breast cancer (TNBC) patients without evaluation of molecular and clinical predictors in several randomized clinical studies. Only fewer than 20{\%} of metastatic TNBCs showed response to anti-EGFR therapy. In order to increase the overall response rate, first step would be to classify TNBC into good or poor responders according to oncogenic mutation profiles. This study provides the molecular characteristics of TNBCs including EGFR gene copy number changes and mutation status of EGFR and KRAS gene in Korean TNBC patients. Mutation analysis for EGFR, KRAS, BRAF and TP53 from a total of 105 TNBC tissue samples was performed by direct sequencing, peptide nucleic acid-mediated PCR clamping method and real-time PCR. Copy number changes of EGFR gene were evaluated using multiplex ligation-dependent probe amplification. Out of all 105 TNBCs, 15.2{\%} (16/105) showed EGFR copy number changes. Among them, increased or decreased EGFR copy number was detected in 13 (5 single copy gain, 2 amplification and 4 high-copy number amplification) and 3 cases (3 hemizygous deletion), respectively. The mutation frequencies of KRAS, EGFR and TP53 gene were 1.9{\%} (G12V and G12D), 1.0{\%} (exon 19 del) and 31.4{\%}, respectively. There was no BRAF V600E mutation found. Future studies are needed to evaluate the clinical outcomes of TNBC patients who undergo anti-EGFR therapy according to the genetic status of EGFR.",
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Spectrum of EGFR gene copy number changes and KRAS gene mutation status in korean triple negative breast cancer patients. / Kim, Yoonjung; Kim, Juwon; Lee, Hy De; Jeong, Joon; Lee, Woochang; Lee, Kyung A.

In: PloS one, Vol. 8, No. 10, e79014, 30.10.2013.

Research output: Contribution to journalArticle

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