title: A case of early onset rectal cancer of Lynch syndrome with a novel deleterious PMS2 mutation.
abstract: Heterozygous deleterious mutation of the PMS2 gene is a cause of Lynch syndrome, an autosomal dominant cancer disease. However, the frequency of PMS2 mutation is rare compared with that of the other causative genes; MSH2, MLH1 and MSH6. PMS2 mutation has so far only been reported once from a Japanese facility. Detection of PMS2 mutation is relatively complicated due to the existence of 15 highly homologous pseudogenes, and its gene conversion event with the pseudogene PMS2CL. Therefore, for PMS2 mutation analysis, it is crucial to clearly distinguish PMS2 from its pseudogenes. We report here a novel deleterious 11 bp deletion mutation of exon 11 of PMS2 distinguished from PMS2CL in a 34-year-old Japanese female with rectal cancer. PMS2 mutated at c.1492del11 results in a truncated 500 amino acid protein rather than the wild-type protein of 862 amino acids. This is supported by the fact that, although there is usually concordance between MLH1 and PMS2 expression, cells were immunohistochemically positive for MLH1, whereas PMS2 could not be immunohistochemically stained using an anti-C-terminal PMS2 antibody, or effective PMS2 mRNA degradation with NMD caused by the frameshift mutation.
authors.affiliation: Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo Department of Clinical Research, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors.forename: Sachio
authors.initials: S
authors.lastname: Nomura
authors.affiliation: Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors.forename: Yuumi
authors.initials: Y
authors.lastname: Ashihara
authors.affiliation: Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kita
authors.affiliation: Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors.forename: Junya
authors.initials: J
authors.lastname: Yamaguchi
authors.affiliation: Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Clinical Genetic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo marai@jfcr.or.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Arai
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D000070976:Mismatch Repair Endonuclease PMS2; D017384:Sequence Deletion
chemical_list: D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes
keywords: Lynch syndrome; PMS2; PMS2CL; frameshift mutation