TP53 codon 72 polymorphism is associated with FGFR3 and RAS mutation in non-muscle-invasive bladder cancer

TP53, a well-known tumor-suppressor gene in bladder carcinogenesis, has a functional single-nucleotide polymorphism on codon 72. The aim of this study was to elucidate the association between TP53 codon 72 polymorphism and somatic mutations in bladder cancer. Germline TP53 codon 72 polymorphism and...

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Bibliographic Details
Published in:	PloS one 2019-08, Vol.14 (8), p.e0220173
Main Authors:	Kawahara, Takashi, Kojima, Takahiro, Kandori, Shuya, Kurobe, Masahiro, Yoshino, Takayuki, Kimura, Tomokazu, Nagumo, Yoshiyuki, Ishituka, Ryutaro, Mitsuzuka, Koji, Narita, Shintaro, Kobayashi, Takashi, Matsui, Yoshiyuki, Ogawa, Osamu, Sugimoto, Mikio, Miyazaki, Jun, Nishiyama, Hiroyuki
Format:	Article
Language:	eng
Subjects:	Adult Aged Aged, 80 and over Alleles Apoptosis Biology and Life Sciences Biomarkers, Tumor - genetics Bladder Bladder cancer Cancer Cancer genetics Cancer patients Carcinogenesis Carcinogens Care and treatment Cell cycle Codons Epidermal growth factor Female Fibroblast growth factor receptor 1 Fibroblast growth factor receptors Fibroblasts Follow-Up Studies Gene expression Gene frequency Gene mutation Gene mutations Gene polymorphism Gene sequencing Genes Genetic aspects Genetic polymorphisms Genotyping Humans Invasiveness Kinases Lung cancer Male Medicine Medicine and Health Sciences Metastasis Middle Aged Molecular modelling Muscles Mutation Neoplasm Invasiveness Nucleotides p53 Protein Polymorphism Polymorphism, Single Nucleotide Prognosis Prospective Studies ras Proteins - genetics Receptor, Fibroblast Growth Factor, Type 3 - genetics Ribonucleic acid RNA RNA sequencing Signal transduction Single nucleotide polymorphisms Single-nucleotide polymorphism Skin cancer Tumor proteins Tumor Suppressor Protein p53 - genetics Tumors Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology Urology
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Summary:	TP53, a well-known tumor-suppressor gene in bladder carcinogenesis, has a functional single-nucleotide polymorphism on codon 72. The aim of this study was to elucidate the association between TP53 codon 72 polymorphism and somatic mutations in bladder cancer. Germline TP53 codon 72 polymorphism and somatic mutations of 50 cancer-associated genes were analyzed in 103 bladder cancer patients (59 non-muscle-invasive and 44 muscle-invasive), using Taqman genotyping assay and target sequencing, respectively. The expression of FGF-FGFR signaling pathway genes was analyzed by RNA sequencing of frozen tissue. The allele frequency of TP53 codon 72 in our cohort was 37, 42, and 21% for Arg/Arg, Arg/Pro, and Pro/Pro, respectively. Interestingly, the prevalence of FGFR3 mutation was higher in patients with the Arg allele, whereas that of the RAS mutation was higher in patients without the Arg allele. The same association was seen in non-muscle-invasive bladder cancer (NMIBC) patients and no differences were observed in muscle-invasive bladder cancer patients. In NMIBC, FGFR1 expression was higher in patients without the Arg allele and FGFR3 expression was higher in patients with the Arg allele. The germline TP53 codon 72 polymorphism was associated with mutations of FGFR3 or RAS and expression of FGFR1 and FGFR3 in NMIBC. These findings provide new insight into the molecular mechanisms underlying the influence of the genetic background on carcinogenesis in bladder cancer.
ISSN:	1932-6203 1932-6203