title: MET Y1253D-activating point mutation and development of distant metastasis in advanced head and neck cancers.
abstract: We investigated if the MET-activating point mutation Y1253D influences clinical outcomes in patients with advanced squamous cell carcinoma of the head and neck (HNSCC). The study population consisted of 152 HNSCC patients treated by hyperfractionated radiotherapy alone or concomitant with chemotherapy between September 1994 and July 2000. Tumors were screened for the presence of the MET-activating point mutation Y1253D. Seventy-eight patients (51%) received radiotherapy alone, 74 patients (49%) underwent radiotherapy concomitant with chemotherapy. Median patient age was 54 years and median follow-up was 5.5 years. Distant metastasis-free survival, local relapse-free survival and overall survival were compared with MET Y1253D status. During follow-up, 29 (19%) patients developed distant metastasis. MET Y1253D was detected in tumors of 21 out of 152 patients (14%). Distant metastasis-free survival (P = 0.008) was associated with MET Y1253D. In a multivariate Cox regression model, adjusted for T-category, only presence of MET Y1253D was associated with decreased distant metastasis-free survival: hazard ratio = 2.5 (95% confidence interval: 1.1, 5.8). The observed association between MET Y1253D-activating point mutation and decreased distant metastasis-free survival in advanced HNSCC suggests that MET may be a potential target for specific treatment interventions.
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland.
authors.forename: Pirus
authors.initials: P
authors.lastname: Ghadjar
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Blank-Liss
authors.forename: Mathew
authors.initials: M
authors.lastname: Simcock
authors.forename: Ivan
authors.initials: I
authors.lastname: Hegyi
authors.forename: Karl T
authors.initials: KT
authors.lastname: Beer
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Aebersold
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Zimmer
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D017931:DNA Primers; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000235:genetics*
chemical_list: D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met