Abstract
Lynch syndrome, a familial cancer syndrome causing colorectal and other cancers, is caused by mutations in the MLH1, MSH2, MSH6, or PMS2 genes. Germline PMS2 testing has only recently become available, and there is no professional consensus regarding the circumstances under which PMS2 testing should be offered to patients. Although PMS2 mutations are not considered to account for a large percentage of Lynch syndrome cases, some authors have suggested that since PMS2 germline testing is not routinely offered to patients with suspected Lynch syndrome, the frequency of PMS2 mutations may be underestimated. The aim of this study was to assess current PMS2 testing practices among genetic counselors who see patients for cancer risk assessment, by exploring factors that influence their decision to offer the test, the sequence in which Lynch-related tests are most commonly offered, and recommendations for future testing. We recruited genetic counselors who had counseled for Lynch syndrome in the past year through the National Society of Genetic Counselors, the NSGC Cancer Special Interest Group, and the Canadian Association of Genetic Counselors listservs to complete an anonymous, online survey. We received 80 completed surveys, including 60 from genetic counselors who had personally offered PMS2 germline testing. Among the counselors who reported having offered PMS2 testing, we found that PMS2 full sequencing and deletion/duplication testing was offered, on average, in 19% and 12%, of their total Lynch syndrome cases, respectively. Most genetic counselors reported offering MSI and IHC for all 4 Lynch-causing genes simultaneously, followed by MLH1, MSH2, and MSH6 germline testing. PMS2 germline testing was considered only in the absence of a positive finding from MLH1, MSH2 and MSH6 testing. Overall, our findings suggest that genetic counselors do not view PMS2 germline testing as a first tier test for individuals being evaluated for Lynch syndrome.