Metastatic colorectal adenocarcinoma tumor purity assessment from whole exome sequencing data.

Tumors rich in stroma are associated with advanced stage and poor prognosis in colorectal adenocarcinoma (CRC). Abundance of stromal cells also has implications for genomic analysis of patient tumors as it may prevent detection of somatic mutations. As part of our efforts to interrogate stroma-cancer cell interactions and to identify actionable therapeutic targets in metastatic CRC, we aimed to determine the proportion of stroma embedded in hepatic CRC metastases by performing computational tumor purity analysis based on whole exome sequencing data (WES). Unlike previous studies focusing on histopathologically prescreened samples, we used an unbiased in-house collection of tumor specimens. WES from CRC liver metastasis samples were utilized to evaluate stromal content and to assess the performance of three in silico tumor purity tools, ABSOLUTE, Sequenza and PureCN. Matching tumor derived organoids were analyzed as a high purity control as they are enriched in cancer cells. Computational purity estimates were compared to those from a histopathological assessment conducted by a board-certified pathologist. According to all computational methods, metastatic specimens had a median tumor purity of 30% whereas the organoids were enriched for cancer cells with a median purity estimate of 94%. In line with this, variant allele frequencies (VAFs) of oncogenes and tumor suppressor genes were undetectable or low in most patient tumors, but higher in matching organoid cultures. Positive correlation was observed between VAFs and in silico tumor purity estimates. Sequenza and PureCN produced concordant results whereas ABSOLUTE yielded lower purity estimates for all samples. Our data shows that unbiased sample selection combined with molecular, computational, and histopathological tumor purity assessment is critical to determine the level of stroma embedded in metastatic colorectal adenocarcinoma.

Type D personality is associated with psychological distress and poor self-rated health among the elderly: a population-based study in Japan.

We investigated the association between Type D personality, psychological distress, and self-ratings of poor health in elderly Japanese people. In August 2010, questionnaires were sent to all residents aged ≥65 in three municipalities (n = 21232) in Okayama Prefecture, Japan, and. 13929 questionnaires were returned (response rate: 65.6%). To assess mental and physical health outcomes, we used the Kessler Psychological Distress Scale and a single item question regarding perceived general health. We analyzed 9759 questionnaires to determine odds ratios (ORs) and 95% confidence intervals (CIs) for several health outcomes, adjusting for sex, age, smoking status, frequency of alcohol consumption, overweight status, educational attainment, socioeconomic status, and number of cohabiters. The multiple imputation method was employed for missing data regarding Type D personality. The prevalence of Type D personality in our sample was 46.2%. After adjusting for covariates, we found that participants with Type D personality were at 4-5 times the risk of psychological distress, and twice the risk of poor self-rated health. This association was stronger in participants aged 65-74 years (psychological distress; OR: 5.80, 95% CI: 4.96-6.78, poor self-rated health; OR: 2.84, 95% CI: 2.38-3.38) than in those aged over 75 years (psychological distress; OR: 4.54, 95% CI: 3.96-5.19, poor self-rated health; OR: 2.05, 95% CI: 1.79-2.34). Type D personality is associated with adverse health status among Japanese elderly people in terms of mental and physical risk; therefore, further research into the implications of this personality type is warranted.