Prevalence and clinical impact of Met Y1253D-activating point mutation in radiotherapy-treated squamous cell cancer of the oropharynx.

作者: Daniel M Aebersold , Olfert Landt , Sylvie Berthou , Günther Gruber , Karl T Beer

DOI: 10.1038/SJ.ONC.1206968

关键词: CancerAngiogenesisPoint mutationRadiation therapyMetastasisCarcinogenesisImmunologyBiologyHepatocyte Growth Factor ReceptorHead and neck cancerCancer research

摘要: Aberrant signalling through the hepatocyte growth factor/scatter factor receptor Met has been implicated in various aspects of development human cancer including promotion tumour invasion, angiogenesis and metastasis. Moreover, experimental data indicate that activation may be involved cellular resistance towards antineoplastic treatments such as chemotherapy ionizing radiation. We determined prevalence clinical impact Met-activating mutation Y1253D patients with squamous cell oropharynx treated by radical radiotherapy. To screen archival tissue for presence a low-abundance point mutation, we developed sensitive screening method using real-time polymerase chain reaction along peptide nucleic acid-based DNA clamping melting curve analysis. By this approach, was detected tumours 15 out 138 (10.9%). Both univariate multivariate survival analysis revealed to significantly associated impaired local control. Our results provide evidence is present notable subset oropharyngeal it interfere radioresponsiveness these tumours, supporting notion aberrant potential target radiosensitization.

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