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

  • Luca Morandi
  • Dario de Biase
  • Michela Visani
  • Adriana Monzoni
  • Annalisa Tosi
  • Mauro Brulatti
  • Daniela Turchetti
  • Paola Baccarini
  • Giovanni Tallini
  • Annalisa Pession
Original Article

Abstract

Purpose

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.

Keywords

MSI MT1X MT1XT20 Mononucleotide repeat Microsatellite instability 

Abbreviations

dMMR

Defective mismatch repair

MSI-H

High microsatellite instability

CRC

Colorectal cancer

MT1XT20

3′UTR T20 mononucleotide repeat of the metallothionein 1X gene

MSI-L

Low microsatellite instability

MSS

Microsatellite stability

NCI/ICG-HNPCC

National Cancer Institute/International Collaborative Group-Hereditary Non-Polyposis Colorectal Cancer

AJCC/UICC

American Joint Cancer Committee/Union Internationale Contre le Cancer

FFPE

In formalin fixed and paraffin embedded

H&E

Haematoxylin and eosin

LOH

Loss of heterozygosity

Supplementary material

384_2011_1365_MOESM1_ESM.xls (60 kb)
ESMMSI status in detail for our series: sheet 1 (MSI-high) is a list of all 40 MSI-H specimens; sheet 2 (MSI-low) is a list of all 46 MSI-L specimens. MSI microsatellite instability, MSS microsatellite stability, LOH loss of heterozygosity, AI allelic imbalance, NA not available (XLS 59 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Luca Morandi
    • 1
    • 6
  • Dario de Biase
    • 2
    • 1
  • Michela Visani
    • 2
    • 1
  • Adriana Monzoni
    • 3
  • Annalisa Tosi
    • 1
  • Mauro Brulatti
    • 4
  • Daniela Turchetti
    • 5
  • Paola Baccarini
    • 1
  • Giovanni Tallini
    • 1
  • Annalisa Pession
    • 2
  1. 1.Department of Haematology and Oncological Sciences L. and A. Seragnoli, Section of Anatomic Pathology at Bellaria HospitalUniversity of BolognaBolognaItaly
  2. 2.Department of Experimental PathologyUniversity of BolognaBolognaItaly
  3. 3.Alphagenics Diaco Biotechnologies S.r.l.BasovizzaItaly
  4. 4.General SurgeryBellaria Hospital A.U.S.L. BolognaBolognaItaly
  5. 5.Medical Genetics Unit, Polyclinic S. Orsola-MalpighiUniversity of BolognaBolognaItaly
  6. 6.Sezione di Anatomia Patologica “M. Malpighi”, Dipartimento di Ematologia e Scienze Oncologiche “L. e A. Seragnoli”Università di Bologna, Ospedale BellariaBolognaItaly

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