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In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non-MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non-contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test.

Abstract In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non‐MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non‐contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test.

Deficits in cognitive functions that rely on the integrity of the frontal and temporal lobes are characteristic of normative human aging. Due to similar aging phenotypes and homologous cortical organization between nonhuman primates and humans, several species of macaque monkeys are used as models to explore brain senescence. These macaque species are typically regarded as equivalent models of cognitive aging, yet no direct comparisons have been made to support this assumption. Here we used adult and aged rhesus and bonnet macaques ( Macaca mulatta and Macaca radiata ) to characterize the effect of age on acquisition and retention of information across delays in a battery of behavioral tasks that rely on prefrontal cortex and medial temporal lobe networks. The cognitive functions that were tested include visuospatial short-term memory, object recognition memory, and object-reward association memory. In general, bonnet macaques at all ages outperformed rhesus macaques on tasks thought to rely primarily on the prefrontal cortex, and were more resilient to age-related deficits in these behaviors. On the other hand, both species were comparably impaired by age on tasks thought to preferentially engage the medial temporal lobe. Together, these results suggest that rhesus and bonnet macaques are not equivalent models of cognitive aging and highlight the value of cross-species comparisons. These observations should enable improved design and interpretation of future experiments aimed at understanding changes in cognition across the lifespan. [ABSTRACT FROM AUTHOR]

Background Biopharmaceutical development necessitates use of non-human primates in toxicology, leading to adoption of non-traditional methods including cognitive function assessment. Methods A two-object discrimination and reversal test in cynomolgus monkeys ( Macaca fascicularis) was performed using a Wisconsin General Testing Apparatus ( WGTA). Non-clinical study design and regulatory considerations dictate that infants are raised by their biological mothers until weaning at 6 months. Thirty-four animals (6-21 months of age) were trained to discriminate between two randomly selected stimulus objects to retrieve a reward. Following training, days to first reversal after interchanging the reward were measured. Results Both sexes acquired visual discrimination skills at similar rates. Trends in learning and reversals completed were uniform across age groups. Completing training early in some subjects had no impact on subsequent testing phases. Conclusions Weaned cynomolgus monkey infants can be successfully tested for cognitive abilities using the WGTA in a non-clinical laboratory setting. [ABSTRACT FROM AUTHOR]