Genetic testing for germline STK11 mutations is currently offered at four clinical laboratories.1-29-1 DNA specimens isolated from peripheral blood or the buccal mucosa can be tested utilizing either genetic sequencing of the entire coding region, mutation scanning (e.g., SSCP, DHLPC, DGGE, etc.), or mutation analysis (i.e., assessment for specific mutations). The variability in the types of STK11 mutations identified in PJS families to date suggests that no single currently available mutation analysis technique is likely to be 100% accurate in identifying STK11 mutations. In addition, at least a subset of PJS families appear to have pathogenic mutations outside of the coding region for the gene, suggesting some mutations will be missed with routine methods used currently in the clinical labs that offer testing. One laboratory also offers prenatal diagnosis. Assaying for loss STK11 expression by immunostaining PJS polyps or cancers has also been proposed as a diagnostic method; however, the accuracy of STK11 immunostaining for the detection of STK11 germline mutation carriers is unknown at this time. In fact, Wei et al., demonstrated that the expression of STK11 in polyps is heterogeneous, even in polyps from a single patient. Furthermore, some polyps and cancers contained both nuclear and cytoplasmic expression of STK11, whereas others showed no evidence of STK11 expression. Thus immunohistochemistry cannot be recommended as an effective adjunct to genetic testing at this time.
The detection rate of STK11 germline mutations using genetic analysis is variable and depends upon whether a tested individual has a positive family history of PJS. Approximately 70% of individuals tested by sequence analysis who have a positive family history will harbor disease-causing mutations of STK11.[3-5,14] If a specific STK11 mutation has been previously identified in an affected family member, other family members can be tested with accuracy approaching 100%. The detection rate of STK11 mutations appears to be lower in individuals without a known family history, ranging from 20% to 70%.[3,13]
In general, genetic testing is informative in two situations: 1) to predict whether an ''at-risk'' asymptomatic individual has inherited PJS already clinically diagnosed in a family member; or 2) to confirm the diagnosis of PJS in a patient where the clinical diagnosis is uncertain. Testing of at-risk, asymptomatic family members (which typically involves pre- and posttest genetic counseling) might provide useful information relating to age of onset of PJS, as certain mutations may predispose to earlier development of the syndrome. Additionally, patients harboring distinct STK11 mutations might have an elevated cancer risk. Testing children for PJS (which can become clinically manifest early in life) is similarly available after an STK11 mutation has been identified in an affected family member. In all of these cases, genetic testing may allow individuals and their physicians to devise strategies regarding treatment and future cancer surveillance. Prenatal testing for PJS is currently available, although uncommonly performed.
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