Abstract
Hereditary non-polyposis colorectal cancer (HNPCC) also known as Lynch Syndrome (LS), is a hereditary form of colorectal cancer (CRC). LSis caused by mutations in the mismatch repair (MMR) genes, mostly in MLH1, MSH2, MSH6 and PMS2. Identification of these gene mutations is essential to diagnose CRC, especially at a young age to increase the survival rate. Using open target platform, we have performed genetic association studies to analyze the different genes involved in the LS and to obtain target for disease evidence. We have also analyzed upstream regulators as target molecules in the data sets. We discovered that MLH1, MSH2, MSH6, PMS2, MLH3, EPCAM, TGFBR2, FBXO11 and PRSS58 were showing most association in LS. Our findings may further enhance the understanding of the hereditaryform of CRC.
Highlights
Lynch syndrome is an autosomal dominant condition caused by many mismatch repair genes including four important genes; MLH1, PMS2, MSH2 and MSH6 [1]
The changes in short microsatellite sequences lead to the microsatellite instability, that is found in the majority of Lynch Syndrome (LS) tumors (>90%) in patients with germ line mutations in mismatch repair (MMR) genes [5]
If the patient tumor DNA is found with microsatellite instability (MSI), it will likely yield a mutation in MMR genes
Summary
Lynch syndrome is an autosomal dominant condition caused by many mismatch repair genes including four important genes; MLH1, PMS2, MSH2 and MSH6 [1]. Mutations in the MMR genes lead to the inactivation or lower efficiency to repair mismatches in DNA that leads to the accumulation of spontaneous mutations mostly consist of the insertions and deletions in short repetitive DNA sequences termed microsatellites. The changes in short microsatellite sequences lead to the microsatellite instability, that is found in the majority of LS tumors (>90%) in patients with germ line mutations in MMR genes [5]. The current strategy before sequencing these MMR genes is to do the microsatellite instability (MSI) testing. The identification of the MMR gene status is very important for surveillance and early intervention especially in the carriers and the family members of the CRC patients, appropriate measure could be taken to limit the disease and improve the survival of the patients and carriers of the disease.
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