title: Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma.
abstract: This study aimed to clarify the genomic factors associated with the diagnosis and prognosis of oral squamous cell carcinoma via next-generation sequencing. We evaluated data from 220 cases of oral squamous cell carcinoma. Genomic DNA was eluted using formalin-fixed, paraffin-embedded samples, and targeted resequencing of 50 cancer-related genes was performed. In total, 311 somatic mutations were detected in 220 patients, consisting of 68 synonymous mutations and 243 non-synonymous mutations. Genes carrying mutations included TP53, CDKN2A, and PIK3CA in 79 (35.9%), 35 (15.9%), and 19 patients (8.6%), respectively. Copy number analysis detected amplification of PIK3CA and AKT1 in 38 (17.3%) and 11 patients (5.0%), respectively. Amplification of receptor tyrosine kinases was found in 37 patients (16.8%). Distant metastasis was noted in nine of 37 patients (24%) with receptor tyrosine kinase amplification, accounting for 43% of the 21 cases of distant metastasis. The cumulative 5-year survival rate was 64.6% in the receptor tyrosine kinase amplification group vs 85.2% in the no receptor tyrosine kinase amplification group. Moreover, we identified significantly poorer prognosis in the TP53 mutation/receptor tyrosine kinase amplification group, for which the cumulative 5-year survival rate was 41.6%. In conclusion, the results of this study demonstrated that receptor tyrosine kinase amplification is a prognostic factor for distant metastasis of oral squamous cell carcinoma, indicating the necessity of using next-generation sequencing in clinical sequencing.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Oikawa
authors.affiliation: Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.|Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kei-Ichi
authors.initials: KI
authors.lastname: Morita
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Kayamori
authors.affiliation: Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.|Genome Laboratory, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Tanimoto
authors.affiliation: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.|Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Harada
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary*; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology*; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: Distant metastasis; gene amplification; next-generation sequencing; oral squamous cell carcinoma; receptor tyrosine kinase