title: Prevalence of low-penetrant germline TP53 D49H mutation in Japanese cancer patients.
abstract: Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline TP53 and found 10 types of non-synonymous single nucleotide variants. In the present study, we focused on 6 patients with germline D49H mutation located in the transactivation domain 2 of p53 protein, since the mutation seemed to be prevalent in cancer patients and to be pathogenic. According to the initial survey for family history of the proband with the germline TP53 D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline TP53 mutation screening. Since this patient possesses double germline mutations of TP53 D49H and A159D, further studies are required to evaluate contribution of the D49H mutation in this morbidity. The remaining 5 patients had family histories of cancer, but none fulfills the criteria either for the Li-Fraumeni/Li-Fraumeni-like syndromes or the 2009 Chompret criteria for germline TP53 mutation screening. It is possible to postulate that the germline TP53 D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline TP53 mutation plays an important role in clinical practice as it will prevent mistaking cancer patients with unusual heredities for sporadic cases.
authors.affiliation: Shizuoka Cancer Center Hospital.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ohnami
authors.forename: Sumiko
authors.initials: S
authors.lastname: Ohnami
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Tohru
authors.initials: T
authors.lastname: Mochizuki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Kouji
authors.initials: K
authors.lastname: Maruyama
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Katagiri
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishida
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takahashi
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Nishimura
authors.forename: Masanori
authors.initials: M
authors.lastname: Terashima
authors.forename: Taiichi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kinugasa
authors.forename: Yushi
authors.initials: Y
authors.lastname: Yamakawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Onitsuka
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugino
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsubayashi
authors.forename: Yasue
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Maki
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Kengo
authors.initials: K
authors.lastname: Inoue
authors.forename: Kimiko
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Misato
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Uesaka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003062:Codon; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53