title: Common and complex Notch1 mutations in Chinese oral squamous cell carcinoma.
abstract: OBJECTIVE
  To determine Notch1 mutation status in oral squamous cell carcinoma (OSCC) from Chinese population and its potential clinical implications.
  
  
  METHODS
  Surgically resected OSCC tissues from 51 Chinese patients and 13 head and neck squamous cell carcinoma (HNSCC) cell lines were sequenced for mutations in the entire coding regions of Notch1 and TP53 using a next-generation sequencing platform. Sequences of the genes were also determined in corresponding normal tissues from 46 of the 51 patients. Mutations and their association with clinical parameters were analyzed.
  
  
  RESULTS
  Six mutations in Notch1 and 11 mutations in TP53 coding regions were detected in 4 (31%) and 10 (77%) of the 13 HNSCC cell lines, respectively. Forty-two somatic Notch1 mutations, including 7 nonsense mutations and 11 mutations within the domain commonly harboring potential activating mutations in acute lymphoblastic leukemia, were detected in 22 (43%) of the 51 Chinese OSCC tumors. In comparison, 25 somatic TP53 mutations were observed in 21 (41%) of the 51 tumors. Patients whose tumors carried Notch1 mutation had significantly shorter overall and disease-free survivals (P = 0.004 and P = 0.001, respectively, by log-rank test) compared with those whose tumors carried no Notch1 mutation. Multivariate analysis showed that both Notch1 mutation and lymph node metastasis are independent prognostic factors in the patient population (P = 0.001). All 15 patients with both Notch1 mutation and nodal metastasis recurred or metastasized within 2 years after surgery.
  
  
  CONCLUSIONS
  Notch1 mutation is common in Chinese OSCC and associates with clinical outcomes. The complexity of the mutation spectrum warrants further investigation of Notch1 in Chinese patients with OSCC.
authors.affiliation: Authors' Affiliations: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Stomatology, Shanghai, China; Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry; Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore; and Personal Diagnostix Inc., Gaithersburg, Maryland.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Song
authors.forename: Ronghui
authors.initials: R
authors.lastname: Xia
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Long
authors.forename: Hening
authors.initials: H
authors.lastname: Ren
authors.forename: Wantao
authors.initials: W
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D051881:Receptor, Notch1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53