title: Profile of TP53 gene mutations in sinonasal cancer.
abstract: Genetic alterations underlying the development of the cancer of the nose and paranasal sinuses (sinonasal cancer, SNC), a rare cancer that can be included in the group of head and neck cancers, are still largely unknown. We recently reported that TP53 mutations are a common feature of SNC, with an overall frequency of 77%, and they show association to adenocarcinoma and wood-dust exposure [15]. In this study, we report in detail the sequence change for 159 TP53 mutations identified by direct sequencing. More than half of the mutations (60%, 95/159) were missense mutations; there were also 28 (18%) frameshift or nonsense mutations, and 36 (23%) intronic or silent mutations. In coding region, the most common base change detected was C-->T transition (43/125; 34% of base changes in the coding region). G-->T transversions occurred at a frequency of 10% (12/125), which is less than reported in mutation databases for head and neck squamous cell carcinoma (24%). Characteristically, in our SNC series, the mutations were scattered over a large number of codons, codon 248 being the most frequent target of base substitution. Codon 135 was the second most frequently mutated codon; this nucleotide position has not been reported before as frequently mutated in head and neck cancer or human cancer in general. About half of all tumours with TP53 mutations carried more than one mutation. Interestingly, 86% (19/22) of the silent mutations detected had occurred in tumours with multiple mutations.
authors.affiliation: Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Reetta
authors.initials: R
authors.lastname: Holmila
authors.forename: Jette
authors.initials: J
authors.lastname: Bornholdt
authors.forename: Tuula
authors.initials: T
authors.lastname: Suitiala
authors.forename: Diane
authors.initials: D
authors.lastname: Cyr
authors.forename: Michael
authors.initials: M
authors.lastname: Dictor
authors.forename: Torben
authors.initials: T
authors.lastname: Steiniche
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Danièle
authors.initials: D
authors.lastname: Luce
authors.forename: Kirsti
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
mesh_terms: D000393:Air Pollutants / Q000633:toxicity; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D016273:Occupational Exposure; D010255:Paranasal Sinus Neoplasms / Q000235:genetics*; D012907:Smoking; D014934:Wood / Q000009:adverse effects
chemical_list: D000393:Air Pollutants