Research Highlights

Classification of cancer syndrome will help patients

Published online 5 February 2014

Aisha El-Awady

DNA mismatch repair (MMR) recognizes and repairs mutations that disrupt the structure of DNA. Defects in the MMR genes MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome, an inherited condition putting a person at high risk of colon cancer and other cancers of the digestive tract.

The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), undertook a study led by Maurizio Genuardi from the University of Florence in Italy, including Fahd Al-Mulla from Kuwait University in Kuwait City, to establish a standardized classification scheme for MMR gene variants involved in Lynch syndrome, publishing their findings in Nature Genetics.

DNA variations detected in the course of clinical testing of the MMR genes are often of uncertain clinical and functional significance. InSiGHT encouraged researchers to submit unpublished clinical and research data. This was reviewed and systemically evaluated, and a 5-tiered scheme was applied to classify 2,360 unique variants of MMR genes.

The identification of these MMR gene mutations will help improve the clinical management and genetic counselling of cancer patients and their relatives.

"This work can potentially benefit thousands of Lynch syndrome families worldwide, and can serve as a model for other disease-causing genes," says Genuardi.


  1. Thompson, B.A. et al. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nature Genetics (2013) doi:10.1038/ng.2854