The occurrence of Lynch syndrome is due to the involvement of various genes located on different chromosomes. Some mutation accounts for the occurrence of majority of Lynch syndrome expression. All the genes involved in Lynch syndrome are DNA mismatch repair genes.
What Chromosome Is Lynch Syndrome On?
Lynch syndrome, formerly known as hereditary non-polyposis colorectal cancer (HNPCC) is a gene-linked condition involving a variety of genes. The consequence of this disease increases the risk of cancer. The disease is divided into Lynch syndrome 1 which is characterized by the presence of colonic cancer while Lynch syndrome 2 relates to the presence of tumor in extracolonic site which primarily includes ovarian cancer, endometrial cancer, stomach cancer, hepatic cancer and pancreatic cancer. The Lynch syndrome 1 accounts for approximately 5-6% of the total colorectal cancer. It is a genetically heterogenous disease involving autosomal dominant features. This means that only a single faulty gene is required to express the consequence of the disease. Following are the various genes involve in the expression of lynch syndrome:
- MLH1 Gene: It is a type of mismatch repair gene which is present on the chromosome 3 and the effects in this gene accounts for approximately 30% of the cases of Lynch syndrome. It mediates protein-protein interaction when there is any mismatch. The mutation in this gene is associated with microsatellite instability.
- MSH2 Gene: It is a type of mismatch repair gene present on chromosome 2. The mutation in this gene results in almost 60% of the Lynch syndrome cases. It is tumor suppressor gene which is involved in DNA repair mechanism.
- MSH6 Gene: This gene is located on the chromosome 2. The mutation in this gene is related to endometrial cancer. The hMSH6 combines with hMSH2 to form a complex which is responsible for DNA mismatch.
- MSH3 Gene: This mismatch repair gene is located on chromosome 5. MSH3 along with MSH2 gene corrects the mispairs during DNA synthesis. These mispairs occur in microsatellites.
- PMS1 Gene: The PMS1 gene is located on chromosome 2. The mutation in this gene leads to the occurrence of hereditary nonpolyposis colorectal cancer 3. It is probably involved in the repair of mismatches in DNA.
- PMS2 Gene: PMS2 gene is located on chromosome 7. It is believed to have latent endonuclease activity. It forms a dimer with MLH1 and the resultant complex interacts with MLH2 to correct the mismatch bases.
- EPCAM Gene: This gene is found on chromosome 2. The mutation in this gene rarely causes Lynch syndrome through indirect mechanism. Mutation in this gene may cause the inactivation of MSH2 gene.
Lynch Syndrome Diagnosis
The diagnosis of the Lynch syndrome is an important factor for reducing the risk of cancer in the patients in which there is a mutation of the DNA mismatch repair genes. As soon as the diagnosis of Lynch syndrome is done on the patients, the next step is to screen the close relatives of the patient for possible hereditary of Lynch syndrome. The strategy is designed to reduce the risk of cancer in these patients. This may be done through periodic examination and screening, surgical intervention, diet, changes in lifestyle and the drugs such as aspirin and oral contraceptives. Following are the diagnostic methods used for diagnosis of Lynch syndrome:
Genetic Screening: Genetic screening of the patient is done by gene mapping and analyzing the presence of any mutation in the genes which are responsible for DNA mismatch repairing.
Tumor Testing: Tumor testing is done for diagnosing the presence of cancer.
Mutation Analysis: Mutation analysis of the patient is done to predict the changes due to mutation.
Various genes are involved in the expression of Lynch syndrome. The genes involved are MLH1 on chromosome 3, MSH2, MSH6 and PMS1 genes situated on chromosome 2, EPCAM situated on chromosome 2, MSH3 on chromosome 5 and PMS2 is situated on chromosome 7. Many of the genes form the dimer complex with other genes and are responsible for correction of any mismatch during DNA synthesis. Mutation of these genes may lead to Lynch syndrome which results in increasing the risk of cancer.