Detection of Microsatellite Instability in Colonoscopic Biopsies and Postal Urine Samples from Lynch Syndrome Cancer Patients Using a Multiplex PCR Assay.

Identification of mismatch repair (MMR)-deficient colorectal cancers (CRCs) is recommended for Lynch syndrome (LS) screening, and supports targeting of immune checkpoint inhibitors. Microsatellite instability (MSI) analysis is commonly used to test for MMR deficiency. Testing biopsies prior to tumour resection can inform surgical and therapeutic decisions, but can be limited by DNA quantity. MSI analysis of voided urine could also provide much needed surveillance for genitourinary tract cancers in LS. Here, we reconfigure an existing molecular inversion probe-based MSI and BRAF c.1799T > A assay to a multiplex PCR (mPCR) format, and demonstrate that it can sample >140 unique molecules per marker from <1 ng of DNA and classify CRCs with 96−100% sensitivity and specificity. We also show that it can detect increased MSI within individual and composite CRC biopsies from LS patients, and within preoperative urine cell free DNA (cfDNA) from two LS patients, one with an upper tract urothelial cancer, the other an undiagnosed endometrial cancer. Approximately 60−70% of the urine cfDNAs were tumour-derived. Our results suggest that mPCR sequence-based analysis of MSI and mutation hotspots in CRC biopsies could facilitate presurgery decision making, and could enable postal-based screening for urinary tract and endometrial tumours in LS patients.

The role of sex, gender, and education on depressive symptoms among young adults in the United States.

BACKGROUND: Men are less likely to experience depression and both women and men who self-assess as high in traits associated with masculinity are less likely to experience depression. Recent theoretical developments stress that the context of gender construction varies by other aspects of social status such as education. METHODS: Data come from the National Longitudinal Study of Adolescent Health Wave III, romantic relationship sub-sample, a nationally representative sample of middle and high school students in the U.S. in 1997. Wave III data were collected in 2001-2002 when they are ages 18-26. A subsample of individuals who were or currently are in a romantic relationship (N=4302) were administered the Bem Sex Role Inventory (BSRI). RESULTS: We find that femininity, not masculinity, results in less depressive symptoms among women regardless of education. Femininity is associated with less depressive symptoms among college educated men, but masculinity is associated with less depressive symptoms among non-college educated men. Sex differences in the association between gender traits and depression symptoms are smaller among those who have attended college. CONCLUSIONS: Results stress the importance of context for understanding the relationship between sex, gender, and depression. Individuals benefit more from both masculinity and femininity with increased education. Conversely, those with less education may be penalized for sex-gender incongruent traits in terms of mental health. LIMITATIONS: These analyses are cross-sectional, making causal inference impossible. This sample is limited to young adults who were or had been in a romantic relationship at the time of the survey.