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Microsatellite instability assay, performed in a patient with hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability is present in the genetic marker shown and three others, confirming genomic instability in the tumor sample. |
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Solid Tumors
Microsatellite Instability
Microsatellite instability (MSI) is detected in 90% of hereditary non-polyposis colon cancer (HNPCC) and 15% of the sporadic colorectal cancers. In many cases, DNA mismatch repair genes such as MSH2, MLH1 and MSH6 are defective. The laboratory performs a multiplex PCR amplification of 5 mononucleotide microsatellite markers; the size distribution of the products compared to normal tissue or peripheral blood leukocytes determines whether microsatellite instability is present. Immunohistochemical correlation is recommended in all cases as a supportive and confirmatory measure as suggested by the American Joint Committee on Cancer.
Hereditary diffuse gastric cancer
CDH1 germline mutations are associated with both hereditary diffuse gastric cancer and lobular breast cancer. The inheritance pattern is autosomal dominant with incomplete penetrance (~80% for diffuse gastric cancer and ~40% for lobular breast cancer). Mutations are widely distributed throughout the gene, and associated with loss of function of the mutated E-cadherin allele. By the time gastric cancer becomes symptomatic, it is rarely curable (<20% 5 year survival). However, a high cure rate (>90% 5 year survival) is possible if the stomach is removed prior to tumor invasion through the gastric wall. Identification of individuals at high risk of developing diffuse gastric cancer affords the opportunity for elective prophylactic gastrectomy. Direct DNA sequencing that covers coding and splice site regions of the CDH1 gene is offered. Because mutations are distributed across all coding exons of the CDH1gene, an analysis of all exons is recommended. For families with a known mutation, sequencing of a single exon may be appropriate.
More information is available on the following website:
http://cancer.stanfordhospital.com/forPatients/services/geneticCounseling/HDGC
