A ten markers panel provides a more accurate and complete microsatellite instability analysis in mismatch repair-deficient colorectal tumors

Marco Agostini, Maria Vittoria Enzo, Luca Morandi, Chiara Bedin, Silvia Pizzini, Silvia Mason, Roberta Bertorelle, Emanuele Urso, Claudia Mescoli, Mario Lise, Salvatore Pucciarelli, Donato Nitti

Research output: Contribution to journalArticle

Abstract

Tumour microsatellite instability (MSI) is useful in identifying patients with hereditary non-polyposis colorectal cancer (HNPCC) with defective DNA mismatch repair (MMR} genes. A reference Bethesda panel has limitations resulting from the inclusion of dinucleotide markers, which are less sensitive and specific for detection of tumours with MMR deficiencies. We developed a multiplex PCR assay with additional four mononucleotide markers and one dinucleotide marker (NR-21, NR-24, BAT-40, TGF-BetaR and D18S58) for a rapid and proper classification of MSI-H, MSI-L and MSS colorectal cancers. Two tetranucleotide markers were added to identify sample mix-ups and/or contamination. Results: all the 44 cases test cases were in agreement with previous classification except for three cases: one case MSI-H-Bethesda unstable only for dinucleotides markers shifted to MSI-L category and two cases MSI-L-Bethesda unstable for mononucleotide markers shifted to MSI-H category. Immunohistochemistry analysis revealed that these two MSI-H cases did not expressed hMLH1 and they were found to be methylated at the MLH1 promoter, while the first one that shifted to MSI-L showed MMR protein expression. Conclusion: a complete panel of ten markers including four dinucleotide and six mononucleotide microsatellites allows accurate evaluation of tumor MSI status.

Original languageEnglish
Pages (from-to)49-61
Number of pages13
JournalCancer Biomarkers
Volume6
Issue number1
DOIs
Publication statusPublished - 2009

Keywords

  • Colorectal cancer
  • Microsatellite instability
  • Mononuclotide repeats

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Genetics

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  • Cite this

    Agostini, M., Enzo, M. V., Morandi, L., Bedin, C., Pizzini, S., Mason, S., Bertorelle, R., Urso, E., Mescoli, C., Lise, M., Pucciarelli, S., & Nitti, D. (2009). A ten markers panel provides a more accurate and complete microsatellite instability analysis in mismatch repair-deficient colorectal tumors. Cancer Biomarkers, 6(1), 49-61. https://doi.org/10.3233/CBM-2009-0118