TY - JOUR
T1 - Profile of TP53 gene mutations in sinonasal cancer
AU - Holmila, Reetta
AU - Bornholdt, Jette
AU - Suitiala, Tuula
AU - Cyr, Diane
AU - Dictor, Michael
AU - Steiniche, Torben
AU - Wolff, Henrik
AU - Wallin, Håkan
AU - Luce, Danièle
AU - Husgafvel-Pursiainen, Kirsti
N1 - Keywords: Air Pollutants; Base Sequence; Carcinoma, Squamous Cell; Genes, p53; Humans; Mutation; Occupational Exposure; Paranasal Sinus Neoplasms; Smoking; Wood
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.mrfmmm.2009.12.003
DO - 10.1016/j.mrfmmm.2009.12.003
M3 - Journal article
C2 - 20025891
SN - 0027-5107
VL - 686
SP - 9
EP - 14
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -
