Mutation analysis of genes in the EGFR pathway in Head and Neck cancer patients: implications for anti-EGFR treatment response

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• 作者：Carolien Boeckx (1)
  Christine Weyn (1)
  Isabelle Vanden Bempt (2)
  Vanessa Deschoolmeester (1)
  An Wouters (1)
  Pol Specenier (3)
  Carl Van Laer (4)
  Danielle Van den Weyngaert (5)
  Mark Kockx (2)
  Jan B Vermorken (3)
  Marc Peeters (1) (3)
  Patrick Pauwels (1) (6)
  Filip Lardon (1)
  Marc Baay (1)
  
  1. Center for Oncological Research (CORE) Antwerp ; Laboratory of Cancer Research and Clinical Oncology ; University of Antwerp ; Wilrijk ; Belgium
  2. HistoGeneX ; Berchem ; Belgium
  3. Department of Medical Oncology ; Antwerp University Hospital ; Edegem ; Belgium
  4. Department of Otolaryngology ; Antwerp University Hospital ; Edegem ; Belgium
  5. Department of Radiation Therapy ; Antwerp University Hospital ; Edegem ; Belgium
  6. Department of Pathology ; Antwerp University Hospital ; Edegem ; Belgium
  
• 关键词：Head neck squamous cell carcinoma ; EGFR inhibitors ; Cetuximab ; Resistance ; KRAS mutations ; EGFRvIII mutations ; EGFR tyrosine kinase mutations ; HPV
• 刊名：BMC Research Notes
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：7
• 期：1
• 全文大小：437 KB
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• 刊物主题：Biomedicine general; Medicine/Public Health, general; Life Sciences, general;
• 出版者：BioMed Central
• ISSN：1756-0500

文摘

Background Targeted therapy against the Epidermal Growth Factor Receptor (EGFR) is among the most promising molecular therapeutics for Head and Neck Squamous Cell Carcinoma (HNSCC). However, drug resistance limits the clinical efficacy of anti-EGFR monoclonal antibodies and no predictive biomarker has entered the clinic yet. Methods A retrospective clinical study was performed utilizing pathological specimens from 52 newly diagnosed HNSCC patients. These patients were screened for mutations in EGFR and KRAS. Tyrosine kinase mutations in EGFR and KRAS mutations were evaluated by high resolution melting analysis (HRMA), whereas EGFRvIII was determined using one-step real-time PCR. Finally, patient samples were screened for HPV-DNA by GP5+/6+ PCR. Survival analysis was performed using Kaplan-Meier analysis and significance was calculated using log-rank statistic. Results In our study population no EGFRvIII mutations were present. However, two silent mutations were found; T785T in exon 20 and R836R in exon 21 of the EGFR gene. Additionally, HRMA revealed an abnormal KRAS melting pattern in 7.0% of the samples. However, the KRAS StripAssay could confirm only one sample with a G12S mutation and none of these samples could be confirmed by direct sequencing. HPV DNA was present in 3/25 larynx and 9/27 oropharynx tumors. Conclusion The low rate of EGFR and KRAS mutations in this Belgian HNSCC population suggests that these genes will probably not play a major role in predicting response to anti-EGFR therapy in HNSCC. Hence, other predictive markers need to be discovered in order to optimize EGFR targeting therapy.