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

Takashi Kawahara, Takahiro Kojima, Shuya Kandori, Masahiro Kurobe, Takayuki Yoshino, Tomokazu Kimura, Yoshiyuki Nagumo, Ryutaro Ishituka, Koji Mitsuzuka, Shintaro Narita, Takashi Kobayashi, Yoshiyuki Matsui, Osamu Ogawa, Mikio Sugimoto, Jun Miyazaki, Hiroyuki Nishiyama

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Objective 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. Material and methods 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. Results 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. Conclusion 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.

Original languageEnglish
Article numbere0220173
JournalPloS one
Volume14
Issue number8
DOIs
Publication statusPublished - 2019 Aug 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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