title: Tongue carcinoma infrequently harbor common actionable genetic alterations.
abstract: BACKGROUND
  Oral tongue squamous cell carcinomas (TSCC) are a unique subset of head and neck cancers with a distinct demographic profile, where up to half of the cases are never smokers. A small proportion of patients with OSCC are known to respond to EGFR TKI. We used a high-sensitivity mass spectrometry-based mutation profiling platform to determine the EGFR mutation status, as well as other actionable alterations in a series of Asian TSCC.
  
  
  METHODS
  66 TSCC patients treated between 1998-2009 with complete clinico-pathologic data were included in this study. Somatic mutation profiling was performed using Sequenom LungCarta v1.0, and correlated with clinical parameters.
  
  
  RESULTS
  Mutations were identified in 20/66(30.3%) of samples and involved TP53, STK11, MET, PIK3CA, BRAF and NRF2. No activating EGFR mutations or KRAS mutations were discovered in our series, where just over a third were never smokers. The most common mutations were in p53 (10.6%; n = 7) and MET (10.6%, n = 11) followed by STK11 (9.1%, n = 6) and PIK3CA (4.5%, n = 3). BRAF and NRF2 mutations, which are novel in TSCC, were demonstrated in one sample each. There was no significant correlation between overall mutation status and smoking history (p = 0.967) or age (p = 0.360). Positive MET alteration was associated with poorer loco-regional recurrence free survival (LRFS) of 11 months [vs 90 months in MET-negative group (p = 0.008)]. None of the other mutations were significantly correlated with LRFS or overall survival. Four of these tumors were propagated as immortalized cell lines and demonstrated the same mutations as the original tumor.
  
  
  CONCLUSIONS
  Using the Sequenom multiplexed LungCarta panel, we identified mutations in 6 genes, TP53, STK11, MET, PIK3CA, BRAF and NRF2, with the notable absence of EGFR and HER2 mutations in our series of Asian OSCC. Primary cell line models recapitulated the mutation profiles of the original primary tumours and provide an invaluable resource for experimental cancer therapeutics.
authors.affiliation: Cancer Therapeutics Research Laboratory, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore. daniel.tan.s.w@nccs.com.sg.
authors.forename: Daniel S W
authors.initials: DS
authors.lastname: Tan
authors.forename: Weining
authors.initials: W
authors.lastname: Wang
authors.forename: Hui Sun
authors.initials: HS
authors.lastname: Leong
authors.forename: Pui Hoon
authors.initials: PH
authors.lastname: Sew
authors.forename: Dawn P
authors.initials: DP
authors.lastname: Lau
authors.forename: Fui Teen
authors.initials: FT
authors.lastname: Chong
authors.forename: Sai Sakktee
authors.initials: SS
authors.lastname: Krisna
authors.forename: Tony K H
authors.initials: TK
authors.lastname: Lim
authors.forename: N Gopalakrishna
authors.initials: NG
authors.lastname: Iyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D014062:Tongue Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D055815:Young Adult