title: Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study.
abstract: OBJECTIVE
  The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC).
  
  
  METHODS
  A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations.
  
  
  RESULTS
  The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared the distribution of the mismatch repair mutations in our study population with that in a control group, including all pathogenic mismatch repair mutations of the International Society for Gastrointestinal Hereditary Tumours database (excluding those in our study population). In patients with MSH2 mutations, patients with HNPCC-associated SBCs had fewer mutations in the MutL homologue interaction domain (2.9% versus 19.9%, P = 0.019) but an increased frequency of mutations in codons 626 to 733, a domain that has not previously been associated with a known function, versus the control group (26.5% versus 2.8%, P < 0.001).
  
  
  CONCLUSIONS
  In HNPCC patients, SBC can be the first and only cancer and may develop as soon as the early teens. The distribution of MSH2 mutations found in patients with HNPCC-associated SBCs significantly differed from that found in the control group (P < 0.001).
authors.affiliation: Korean Hereditary Tumor Registry, Laboratory of Cell Biology, Cancer Research Institute and Cancer Research Center, Seoul National University College of Medicine, Korea. jgpark@plaza.snu.ac.kr
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Hong
authors.forename: Byung-Ho
authors.initials: BH
authors.lastname: Nam
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Shin
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Hong
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Seok-Byung
authors.initials: SB
authors.lastname: Lim
authors.forename: Melyssa
authors.initials: M
authors.lastname: Aronson
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Bisgaard
authors.forename: Gregor J
authors.initials: GJ
authors.lastname: Brown
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chow
authors.forename: Peggy
authors.initials: P
authors.lastname: Conrad
authors.forename: Fiona
authors.initials: F
authors.lastname: Douglas
authors.forename: Malcolm
authors.initials: M
authors.lastname: Dunlop
authors.forename: James
authors.initials: J
authors.lastname: Ford
authors.forename: Marc S
authors.initials: MS
authors.lastname: Greenblatt
authors.forename: Jarvinen
authors.initials: J
authors.lastname: Heikki
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
authors.forename: Elly L
authors.initials: EL
authors.lastname: Lynch
authors.forename: Finlay
authors.initials: F
authors.lastname: Macrae
authors.forename: Wendy C
authors.initials: WC
authors.lastname: McKinnon
authors.forename: Gabriela
authors.initials: G
authors.lastname: Möeslein
authors.forename: Benedito Mauro
authors.initials: BM
authors.lastname: Rossi
authors.forename: Paul
authors.initials: P
authors.lastname: Rozen
authors.forename: Lyn
authors.initials: L
authors.lastname: Schofield
authors.forename: Carlos
authors.initials: C
authors.lastname: Vaccaro
authors.forename: Hans
authors.initials: H
authors.lastname: Vasen
authors.forename: Mary
authors.initials: M
authors.lastname: Velthuizen
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
authors.forename: Juul
authors.initials: J
authors.lastname: Wijnen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004379:Duodenal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007078:Ileal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D007580:Jejunal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D011237:Predictive Value of Tests; D011795:Surveys and Questionnaires
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes