title: Partial duplication of MSH2 spanning exons 7 through 14 in Lynch syndrome.
abstract: BACKGROUND
  Lynch syndrome, also referred to as hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer, and is associated with a high incidence of multiple primary neoplasms in various organs.
  
  
  METHODS
  A 79-year-old woman (patient 1) diagnosed with ascending colon cancer had a history of previous carcinomas of the uterus, stomach, uroepithelial tract, and colon. One year later, she developed a brain tumor (glioblastoma). A 54-year-old female (patient 2) was diagnosed with endometrial cancer and sigmoid colon cancer. Both patients underwent genetic evaluations independently.
  
  
  RESULTS
  No mutations were found in an exon-by-exon analysis of genomic DNA by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR. However, multiplex ligation-dependent probe amplification (MLPA) identified genomic duplication spanning from exon 7 to exon 14 of the MSH2 gene in both patients. Due to the presence of this characteristic gene duplication, their pedigrees were investigated further, and these showed that they are paternal half-sisters, consistent with paternal inheritance.
  
  
  CONCLUSIONS
  Large genomic duplication from intron 6 through intron 14 in MSH2 is a very rare cause of Lynch syndrome and is difficult to identify with conventional methods. MLPA may be an alternative approach for detecting large-scale genomic rearrangements.
authors.affiliation: Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Shiozawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyakura
authors.forename: Makiko
authors.initials: M
authors.lastname: Tahara
authors.forename: Kazue
authors.initials: K
authors.lastname: Morishima
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kumano
authors.forename: Koji
authors.initials: K
authors.lastname: Koinuma
authors.forename: Hisanaga
authors.initials: H
authors.lastname: Horie
authors.forename: Alan T
authors.initials: AT
authors.lastname: Lefor
authors.forename: Naohiro
authors.initials: N
authors.lastname: Sata
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Gonda
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tamura
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Kokichi
authors.initials: K
authors.lastname: Sugano
mesh_terms: D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D010375:Pedigree
chemical_list: D051718:MutS Homolog 2 Protein