HNPCC/Lynch Syndrome (MSH6) Sequencing and Deletion/Duplication

Background Information for HNPCC/Lynch Syndrome (MSH6) Sequencing and Deletion/Duplication:
Characteristics: Increased risk of colorectal and extra-colonic cancers including endometrial, renal pelvis, ureter, ovary, stomach, small intestine, and hepatobiliary tract.
Incidence: 1-2 percent of colorectal cancer is due to mismatch repair gene mutations.
Inheritance: Autosomal dominant
Penetranceof MSH6 Mutations: Risk of colorectal cancer is 40 percent in men and 20 percent in women up to age 80. Women also have a 40 percent risk for endometrial cancer up to age 80.
Cause: Pathogenic germline MLH1, MSH2, MSH6, and PMS2 gene mutations.
Gene Tested: MSH6
Clinical Sensitivity: Approximately 5 percent of Lynch syndrome is due to MSH6 mutations.
Methodology: Bidirectional sequencing of MSH6 coding regions and intron-exon boundaries; multiplex ligation-dependent probe amplification (MLPA) to detect large MSH6 exonic deletions.
Test Limitations: Diagnostic errors can occur due to rare sequence variations. The breakpoints of large deletions/duplications will not be determined. Regulatory region, deep intronic mutations and mutations in genes other than MSH6 will not be detected. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.