title: Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR.
abstract: OBJECTIVE
  The microsatellite instability (MSI) phenotype is a characteristic of the hereditary nonpolyposis colorectal cancer syndrome as well as approximately 15% of sporadic colon and gastric tumors. It is a valuable diagnostic marker for the identification of hereditary nonpolyposis colorectal cancer cases and may be a molecular predictive marker for the identification of colon cancer patients who benefit from chemotherapy. To evaluate MSI, a reference panel was proposed at an international consensus meeting, comprised of 2 mononucleotide (BAT-25, BAT-26) and 3 dinucleotide repeats. Analysis of BAT-26 is sufficient for detecting the MSI phenotype in most, but not all, cases. Additional results with dinucleotide markers can sometimes lead to incorrect classification of MSI tumors.
  
  
  METHODS
  We describe here a single fluorescent multiplex system comprising 5 quasimonomorphic mononucleotide repeats for the detection of MSI tumors.
  
  
  RESULTS
  None of 184 germline DNA samples, including 56 from African subjects, was found to contain allelic size variations in more than 2 of these markers. In contrast, all MSI tumors showed allelic size variations in 3 or more of the microsatellites. Using this assay, we confirmed (or reclassified in 6 cases) the MSI status of 124 colon and 50 gastric primary tumors and 16 colon cell lines.
  
  
  CONCLUSIONS
  We propose that using a pentaplex polymerase chain reaction system allows accurate evaluation of tumor MSI status of DNA with 100% sensitivity and specificity without the need to match normal DNA. This assay is simpler to use than those involving dinucleotides and is more specific than using BAT-26 alone.
authors.affiliation: INSERM U434, Centre d'Etudes du Polymorphisme Humain, Paris, France.
authors.forename: Nirosha
authors.initials: N
authors.lastname: Suraweera
authors.forename: Alex
authors.initials: A
authors.lastname: Duval
authors.forename: Maryline
authors.initials: M
authors.lastname: Reperant
authors.forename: Christelle
authors.initials: C
authors.lastname: Vaury
authors.forename: Daniela
authors.initials: D
authors.lastname: Furlan
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Barry
authors.initials: B
authors.lastname: Iacopetta
authors.forename: Richard
authors.initials: R
authors.lastname: Hamelin
mesh_terms: D000349:Africa / Q000208:ethnology; D044383:Black People / Q000235:genetics; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005453:Fluorescence; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats; D010297:Paris / Q000208:ethnology; D016133:Polymerase Chain Reaction / Q000379:methods*; D044465:White People / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm