title: T([20]) repeat in the 3'-untranslated region of the MT1X gene: a marker with high sensitivity and specificity to detect microsatellite instability in colorectal cancer.
abstract: OBJECTIVE
  Stratifying patients defective in mismatch repair (dMMR) with high microsatellite instability (MSI-H) in colorectal cancer (CRC) is of increasing relevance and may provide a more tailored approach to CRC adjuvant therapy. Here, we describe the discovery of a new MSI marker for colorectal cancer located in the 3'-untranslated region (3'UTR, T20 mononucleotide repeat) of the metallothionein 1X gene (MT1XT20).
  
  
  METHODS
  We studied 340 consecutive CRCs using three multiplexed polymerase chain reactions amplifying BAT25, BAT26, TGFBR2, MybT22, BAT40, MT1XT20, NR21, NR24, CAT25, D2S123, D5S346, D17S250, D18S58, CSF1PO, D7S820, and D18S51. Fragments length was evaluated by automated capillary electrophoresis.
  
  
  RESULTS
  Based on the NCI/ICG-HNPCC criteria for MSI classification, 40 CRCs were found to be MSI-high (11.8%), 46 (13.5%) CRCs were MSI-low, and 254 CRCs (74.7%) were stable (MSS). MT1XT20 showed very high sensitivity (97.3%) comparable to BAT26 (97.5%) and CAT25 (97.1%) and the best specificity (100%) as well as MybT22 and CAT25. Indeed, MT1XT20 instability was detected in 36 out of 37 cases (97.3%) of MSI-high colorectal cancers, whereas no MT1XT20 alterations were observed in 254 MSS or in 46 MSI-low cases. On the contrary, BAT40 was found to be unstable in 8/46 MSI-low cases, BAT25 in 6/46, BAT26 4/46, NR21 1/46, and NR24 in 1/45.
  
  
  CONCLUSIONS
  Our results suggest that MT1XT20 represents a sensitive and specific marker for MSI testing and could be included in a complete set of MSI markers for the confident identification of familial or sporadic dMMR patients in CRCs.
authors: Department of Haematology and Oncological Sciences L. and A. Seragnoli, Section of Anatomic Pathology at Bellaria Hospital, University of Bologna, via Altura 3, 40139 Bologna, Italy. l.morandi@ausl.bo.it
authors: Luca
authors: L
authors: Morandi
authors: Dario
authors: D
authors: de Biase
authors: Michela
authors: M
authors: Visani
authors: Adriana
authors: A
authors: Monzoni
authors: Annalisa
authors: A
authors: Tosi
authors: Mauro
authors: M
authors: Brulatti
authors: Daniela
authors: D
authors: Turchetti
authors: Paola
authors: P
authors: Baccarini
authors: Giovanni
authors: G
authors: Tallini
authors: Annalisa
authors: A
authors: Pession
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D053843:DNA Mismatch Repair; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D053842:Microsatellite Instability; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D008668:Metallothionein