title: Germline PMS2 mutation screened by mismatch repair protein immunohistochemistry of colorectal cancer in Japan.
abstract: Germline PMS2 gene mutations were detected by RT-PCR/direct sequencing of total RNA extracted from puromycin-treated peripheral blood lymphocytes (PBL) and multiplex ligation-dependent probe amplification (MLPA) analyses of Japanese patients with colorectal cancer (CRC) fulfilling either the revised Bethesda Guidelines or being an age at disease onset of younger than 70 years, and screened by mismatch repair protein immunohistochemistry of formalin-fixed paraffin embedded sections. Of the 501 subjects examined, 7 (1.40%) showed the downregulated expression of the PMS2 protein alone and were referred to the genetic counseling clinic. Germline PMS2 mutations were detected in 6 (85.7%), including 3 nonsense and 1 frameshift mutations by RT-PCR/direct sequencing and 2 genomic deletions by MLPA. No mutations were identified in the other MMR genes (i.e. MSH2, MLH1 and MSH6). The prevalence of the downregulated expression of the PMS2 protein alone was 1.40% among the subjects examined and IHC results predicted the presence of PMS2 germline mutations. RT-PCR from puromycin-treated PBL and MLPA may be employed as the first screening step to detect PMS2 mutations without pseudogene interference, followed by the long-range PCR/nested PCR validation using genomic DNA.
authors: Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.|Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya, Japan.
authors: Kokichi
authors: K
authors: Sugano
authors: Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.|Department of Endoscopy, National Cancer Center Hospital, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Nakajima
authors: Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.|Molecular Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors: Shigeki
authors: S
authors: Sekine
authors: Division of Pathology and Clinical Laboratories, National Cancer Center Research Institute, Tokyo, Japan.
authors: Hirokazu
authors: H
authors: Taniguchi
authors: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya, Japan.
authors: Shinya
authors: S
authors: Saito
authors: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Utsunomiya, Japan.
authors: Masahiro
authors: M
authors: Takahashi
authors: Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.|Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors: Mineko
authors: M
authors: Ushiama
authors: Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.|Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors: Hiromi
authors: H
authors: Sakamoto
authors: Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan.|Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors: Teruhiko
authors: T
authors: Yoshida
mesh_terms: D044466:Asian People / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics*
chemical_list: C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2
keywords: 
  PMS2
  ; Colorectal cancer; Lynch syndrome; immunohistochemistry; mismatch repair gene