Laboratory Medicine Program

Colorectal and Small Bowel Carcinoma: MLH1 promoter methylation

Clinical Decription:
Lynch Syndrome is caused by pathogenic germline variants in the MLH1, PMS2, MSH2 and MSH6 genes. Presence of pathogenic variants in these genes is associated with increased risk for a number of cancers, including colorectal, endometrial, pancreatic, gastroesophageal, gall bladder and hepatobiliary cancers. For patients with tumors that are found to be deficient in expression of these genes by immunohistochemistry, further molecular testing is performed to help rule out Lynch Syndrome. For MLH1/PMS2 deficient tumors, MLH1 promoter hypermethylation is a common reason for loss of MLH1 and detection of promoter hypermethylation indicates that the the likelihood of Lynch Syndrome is low and further testing is not normally recommended. Conversely, if hypermethylation is not detected, further germline testing for Lynch Syndrome may be indicated. Testing is performed using multiplex-ligation probe amplification (MLPA) targeting specific sequences in the MLH1 promoter that are know to be methylated in tumors. In rare cases, Lynch Syndrome may also be caused by constitutional methylation of the MLH1 promoter, and testing of germline samples can be considered by request.

Method: PCR-MLPA/MS-MLPA

Component Tests Used: n/a

Reference Ranges Used:
Reference ranges for this test are not available online. However, they are included in all test results. For more information, please call us.

Specimen Type: Paraffin-embedded material (FFPE)/Cytology fluids
Volume: n/a

Shipping: room temperature or 4C

Special Instructions: See requisitions for the full list of available testing and special instructions.

Testing Schedule(s): Please call

Turnaround Time: None

For more information, call 416.340.5227 or 1.866.865.5227