Microsatellite instability in colorectal cancer

Microsatellite instability in colorectal cancer

Authors

  • Gian Luigi de' Angelis Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
  • Lorena Bottarelli Department of Medicine and Surgery, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy
  • Cinzia Azzoni Department of Medicine and Surgery, University of Parma, Parma, Italy
  • Nicola de' Angelis Department of Digestive, Hepatobiliary Surgery and Liver Transplantation, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Est-Créteil, Créteil, France
  • Gioacchino Leandro National Institute of Gastroenterology “S. De Bellis” Research Hospital, Castellana Grotte, Italy
  • Francesco Di Mario Unit of Gastroenterology and Digestive Endoscopy of Parma, University Hospital of Parma, Parma, Italy
  • Federica Gaiani Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
  • Francesca Negri Medical Oncology Unit, University Hospital of Parma, Parma, Italy

Keywords:

microsatellite instability, colorectal cancer, mismatch repair, Lynch Syndrome, prognosis

Abstract

Microsatellites are short tandem repeat DNA sequences of one to tetra base pairs distributed throughout the human genome, both in coding and non-coding regions. Owing to their repeated structure, microsatellites are particularly prone to replication errors that are normally repaired by the Mismatch Repair (MMR) system. MMR is a very highly conserved cellular process, involving many proteins, resulting in the identification, and subsequent repair of mismatched bases, likely to have arisen during DNA replication, genetic recombination or chemical or physical damage. Proteins within the MMR system include MLH1, PMS2, MSH2, MSH6, MLH3, MSH3, PMS1, and Exo1. Deficient MMR (dMMR) results in a strong mutator phenotype known as microsatellite instability (MSI), characterized by widespread length polymorphisms of microsatellite sequences due to DNA polymerase slippage. MSI is recognized as one of the major carcinogenetic pathways of colorectal cancer (CRC): it represents a molecular hallmark of hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome (LS); moreover it is detected in 15% of sporadic colorectal cancers, more often due to an epigenetic inactivation of MLH1. Identification of MSI CRC is important, as MSI may serve as a screening tool for detecting LS, a prognostic marker for patient outcome, and a predictive marker for response to chemotherapy and to immunotherapy.

Downloads

Published

17-12-2018

How to Cite

1.
Microsatellite instability in colorectal cancer. Acta Biomed [Internet]. 2018 Dec. 17 [cited 2024 Jun. 14];89(9-S):97-101. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/7960

Most read articles by the same author(s)

1 2 3 4 5 6 > >>