title: Evaluation of MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker for Characterizing Microsatellite Instability in Persian Lynch Syndrome Patients.
abstract: BACKGROUND
  Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynch syndrome) or sporadic, demonstrate better prognosis and altered response to 5FU chemotherapy. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of being categorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using a cohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using just a single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients. A Promega five-marker MSI testing panel and immunohistochemistry (IHC) were used as the gold standard in conjunction with MT1XT20.
  
  
  METHODS
  Colorectal patients with a positive history of familial cancers were selected by evaluating medical records. Based on Amsterdam II criteria for Lynch syndrome 20 families were short listed. DNA was extracted from formalin fixed paraffin embedded tumour and adjacent normal tissues resected from the index case in each family. Extracted DNA was subjected to MT1XT20 mononucleotide marker analysis and assessment with a commercially available five marker MSI testing kit (Promega, USA). IHC also was performed on tissue sections and the results were compared with PCR based data.
  
  
  RESULTS
  Eight (40%), seven (35%) and five (25%) cases were MSI positive using with the Promega kit, IHC and MT1XT20, respectively. Among the markers included in Promega kit, BAT26 marker showed instability in all 8 samples. NR24 and NR21 markers showed instability in 7 (87.5%), and BAT25 and MONO 27 in 6 (75%) and 5 (62.5%).
  
  
  CONCLUSIONS
  Although MT1XT20 was earlier reported as a valid standalone marker for MSI testing in CRC patients, we could not verify this in our Iranian patients. Instead BAT26 among the markers included in Promega MSI testing kit showed instability in all 8 MSI-H CRC samples. Therefore, it seems BAT26 could act well as a single marker for MSI testing in Iranian CRC patients.
authors: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Hezarjarib street, Isfahan, Iran E-mail : r_salehi@med.mui.ac.ir.
authors: Najmeh
authors: N
authors: Farahani
authors: Parvaneh
authors: P
authors: Nikpou
authors: Mohammad Hassan
authors: MH
authors: Emami
authors: Morteza
authors: M
authors: Hashemzadeh
authors: Mehrdad
authors: M
authors: Zeinalian
authors: Seyed Shervin
authors: SS
authors: Shariatpanahi
authors: Rasoul
authors: R
authors: Salehi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D019071:Persia; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C581554:metallothionein1X, human; D008668:Metallothionein