title: Screening for Lynch Syndrome in Young Colorectal Cancer Patients from Saudi Arabia Using Microsatellite Instability as the Initial Test.
abstract: Lynch Syndrome (LS) is a familial cancer condition caused by germline mutations in DNA mismatch repair genes. Individuals with LS have a greatly increased risk of developing colorectal cancer (CRC) and it is therefore important to identify mutation carriers so they can undergo regular surveillance. Tumor DNA from LS patients characteristically shows microsatellite instability (MSI). Our aim here was to screen young CRC patients for MSI as a first step in the identification of unrecognized cases of LS in the Saudi population.
  
  
  
  Archival tumor tissue was obtained from 284 CRC patients treated at 4 institutes in Dammam and Riyadh between 2006 and 2015 and aged less than 60 years at diagnosis. MSI screening was performed using the BAT-26 microsatellite marker and positive cases confirmed using the pentaplex MSI analysis system. Positive cases were screened for BRAF mutations to exclude sporadic CRC and were evaluated for loss of expression of 4 DNA mismatch repair proteins using immunohistochemistry.
  
  
  
  MSI was found in 33/284 (11.6%) cases, of which only one showed a BRAF mutation. Saudi MSI cases showed similar instability in the BAT-26 and BAT-25 markers to Australian MSI cases, but significantly lower frequencies of instability in 3 other microsatellite markers.
  
  
  
  MSI screening of young Saudi CRC patients reveals that approximately 1 in 9 are candidates for LS. Patients with MSI are strongly recommended to undergo genetic counselling and germline mutation testing for LS. Other affected family members can then be identified and offered regular surveillance for early detection of LS-associated cancers.
authors.affiliation: School of Surgery, University of Western Australia, Perth, Australia E-mail : barry. iacopetta@uwa.edu.au.
authors.forename: Masood
authors.initials: M
authors.lastname: Alqahtani
authors.forename: Fabienne
authors.initials: F
authors.lastname: Grieu
authors.forename: Amerigo
authors.initials: A
authors.lastname: Carrello
authors.forename: Benhur
authors.initials: B
authors.lastname: Amanuel
authors.forename: Miral
authors.initials: M
authors.lastname: Mashour
authors.forename: Rabab
authors.initials: R
authors.lastname: Alattas
authors.forename: Khalid
authors.initials: K
authors.lastname: Alsaleh
authors.forename: Abdulmalik
authors.initials: A
authors.lastname: Alsheikh
authors.forename: Sarah
authors.initials: S
authors.lastname: Alqahtani
authors.forename: Barry
authors.initials: B
authors.lastname: Iacopetta
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012529:Saudi Arabia / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D045643:DNA Repair Enzymes