title: Comprehensive characterization of genes associated with the TP53 signal transduction pathway in various tumors.
abstract: The TP53 signal transduction pathway is an attractive target for cancer treatments. In this study, we conducted a comprehensive molecular evaluation of 907 patients with cancer in Japan to identify genomic alterations in the TP53 pathway. TP53 mutations were frequently detected in many cancers, except melanoma, thymic tumors, gastrointestinal stromal tumors, and renal cancers. The frequencies of non-synonymous single nucleotide variants (SNVs) in the TP53 family members TP63 and TP73 were relatively low, although genes with increased frequencies of SNVs were as follows: PTEN (11.7%) in breast cancer, CDKN2A (11.1 and 9.6%) in pancreas and head and neck cancers, and ATM (18.0 and 11.1%) in liver and esophageal cancers. MDM2 expression was decreased or increased in patients with mutant or wild-type TP53, respectively. CDKN1A expression was increased with mutant TP53 in head and neck cancers. Moreover, TP63 overexpression was characteristically observed in squamous cell carcinomas of the lung, esophagus, and head and neck region. Additionally, overexpression of TP63 and TP73 was frequently observed in thymomas. Our results reveal a spectrum of genomic alterations in the TP53 pathway that is characteristic of many tumor types, and these data may be useful in the trials of targeted therapies.
authors.affiliation: Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. s.onami@scchr.jp.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ohnami
authors.affiliation: Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.|SRL Inc, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.affiliation: Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.|SRL Inc, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Saito
authors.affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Naruoka
authors.affiliation: Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hatakeyama
authors.affiliation: Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Mochizuki
authors.affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.affiliation: Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Ohnami
authors.affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.|Regional Resources Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.affiliation: Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics / Q000378:metabolism; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms; D009928:Organ Specificity / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Cancer; Gene expression profiling; Japanese population; TP53 pathway; Whole exome sequencing