<b>Prevalence of low-penetrant germline </b><i><b>TP53</b></i><b> D49H mutation in Japanese cancer </b><b>patients </b>

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Author(s)

    • YAMAGUCHI Ken
    • Shizuoka Cancer Center Hospital|Shizuoka Cancer Center Research Institute
    • SERIZAWA Masakuni
    • Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute
    • AKIYAMA Yasuto
    • Immunotherapy Division, Shizuoka Cancer Center Research Institute
    • MARUYAMA Kouji
    • Experimental Animal Facility, Shizuoka Cancer Center Research Institute
    • ISHIDA Yuji
    • Division of Pediatrics, Shizuoka Cancer Center Hospital
    • KINUGASA Yusuke
    • Division of Colon and Rectal Surgery, Shizuoka Cancer Center Hospital
    • URAKAMI Kenichi
    • Cancer Diagnostics Research Di-vision, Shizuoka Cancer Center Research Institute
    • YAMAKAWA Yushi
    • Division of Colon and Rectal Surgery, Shizuoka Cancer Center Hospital
    • OHDE Yasuhisa
    • Division of Thoracic Surgery, Shizuoka Cancer Center Hospital
    • ITO Ichiro
    • Division of Pathology, Shizuoka Cancer Center Hospital
    • HORIUCHI Yasue
    • Division of Genetic Counseling, Shizuoka Cancer Center Hospital
    • NAGASHIMA Takeshi
    • Cancer Diagnostics Research Di-vision, Shizuoka Cancer Center Research Institute|SRL Inc.
    • WAKAMATSU Kimiko
    • Office for Patient's Information Protection, Shizuoka Cancer Center Hospital
    • SUGIYAMA Misato
    • Office for Patient's Information Protection, Shizuoka Cancer Center Hospital
    • UESAKA Katsuhiko
    • Office for Patient's Information Protection, Shizuoka Cancer Center Hospital|Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital
    • KUSUHARA Masatoshi
    • Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute|Regional Resources Division, Shizuoka Cancer Center Research Institute
    • SHIMODA Yuji
    • Cancer Diagnostics Research Di-vision, Shizuoka Cancer Center Research Institute|SRL Inc.
    • OHNAMI Shumpei
    • Cancer Diagnostics Research Di-vision, Shizuoka Cancer Center Research Institute
    • OHNAMI Sumiko
    • Cancer Diagnostics Research Di-vision, Shizuoka Cancer Center Research Institute
    • OHSHIMA Keiichi
    • Medical Genetics Division, Shizuoka Cancer Center Research Institute
    • MOCHIZUKI Tohru
    • Medical Genetics Division, Shizuoka Cancer Center Research Institute

Abstract

<p>Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline <i>TP53</i> 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 <i>TP53</i> D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline <i>TP53</i> mutation screening. Since this patient possesses double germline mutations of <i>TP53</i> 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 <i>TP53</i> mutation screening. It is possible to postulate that the germline <i>TP53</i> D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline <i>TP53</i> mutation plays an important role in clinical practice as it will prevent mistaking cancer patients with unusual heredities for sporadic cases.</p>

Journal

  • Biomedical Research

    Biomedical Research 37(4), 259-264, 2016

    Biomedical Research Press

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