title: A TP53-truncating germline mutation (E287X) in a family with characteristics of both hereditary diffuse gastric cancer and Li-Fraumeni syndrome.
abstract: Mutations in CDH1, which encodes E-cadherin, have been associated with hereditary diffuse gastric cancer (HDGC) in Western populations but have not been shown to play a major role in Asians. Recently, a patient with familial gastric cancer (FGC) was shown to harbor a germline mutation in the TP53 gene, which encodes p53 and has been previously associated with Li-Fraumeni Syndrome (LFS). To determine whether mutations in TP53 are associated with FGC in Asians, we screened the entire coding region of TP53 in probands from 23 Korean FGC families. We identified a nonsense (E287X) TP53 germline mutation in a family whose history is compatible with both HDGC and LFS. Two members of this family (SNU-G2) were afflicted with brain tumors, seven with gastric cancers, two with sarcomas, and one with both gastric cancer and a sarcoma. The E287X TP53 mutation segregated with the cancer phenotype in the family members from whom DNA samples were available. To our knowledge, this is the first report of a large family with both HDGC and LFS. Our results suggest that TP53 mutational screening in FGC families should be interpreted with caution because additional TP53 mutation-carrying HDGC families may also show LFS-related phenotypes.
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Hio Chung
authors.initials: HC
authors.lastname: Kang
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Park
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Sang-Geun
authors.initials: SG
authors.lastname: Jang
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Song-Yee
authors.initials: SY
authors.lastname: Han
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lim
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Min Ro
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Research Institute and Hospital, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang, Gyeonggi, 411-764, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea.|Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, South Korea. park@ncc.re.kr.|Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea. park@ncc.re.kr.|Research Institute and Hospital, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang, Gyeonggi, 411-764, South Korea. park@ncc.re.kr.
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D018389:Codon, Nonsense / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D007723:Korea; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense