POPULATION GENETICS OF EASTERN OYSTER Crassostrea virginica RESTORATION IN THE CHESPEAKE BAY

The strategic release of captive-bred organisms is one of the most popular methods to restore species, but concerns exist regarding genetic impacts on natural populations over the long-term. Slow recovery of depleted eastern oyster C. virginica populations in the Chesapeake Bay prompted a large-scale hatchery-based restoration program consisting of the mass-release of hatchery-produced juveniles from local, wild broodstock. This dissertation characterized the genetic impact of this program, with the overall goal of understanding how characteristics of species life-history interact with hatchery practices to shape genetic variation in populations over short and long-time scales. In Chapter 2, analysis of genetic diversity changes resulting from hatchery production under two spawning designs (mass- and controlled-spawns) revealed substantial reductions in diversity and the number of breeders from parents to offspring, due primarily to high variance in reproductive success among adults in hatchery culture. In Chapter 3, high-resolution genomic data was used in a population genetic analysis comparing diversity of restored reefs in Harris Creek with variable planting histories and husbandry practices to ‘wild’ Chesapeake Bay oyster reefs. While restored reefs showed similar levels of diversity as wild reefs, strong positive relationships between planting frequency or broodstock numbers and genetic diversity were found, suggesting that hatchery practices can significantly impact diversity in natural populations. These genomic data also permitted the investigation of local adaptation and genotype by environment associations which revealed that salinity was correlated with loci putatively under selection, suggesting potential fitness tradeoffs for sourcing non-local broodstock. In Chapter 4, an individual-based model was created using biological and demographic data from Chesapeake Bay oysters to simultaneously evaluate the impact of multiple hatchery practices on natural population genetic diversity over time scales not possible with empirical methods. Overall, hatchery practices had a large effect on genetic diversity in most scenarios, but spawning practices (mass or controlled) and broodstock rotation were more important than broodstock number, suggesting that broodstock-limited programs may have other options to maintain diversity. In summary, these studies advance our understanding of how marine supplementation impacts both neutral and adaptive variation and will provide critical information for future oyster restoration efforts

Clinical and radiologic features of extraskeletal myxoid chondrosarcoma including initial presentation, local recurrence, and metastases

Background: The aim of the study was to evaluate the clinical and imaging features of extraskeletal myxoid chondrosarcoma (EMC) including initial presentation, recurrence, and metastases. Patients and methods. In this institutional review board-approved retrospective study, imaging features of 13 patients with pathologically proven EMC seen from August 1995 to December 2011 were analyzed. The group included 3 women and 10 men and the mean age was 54 years (range 29–73 years). Imaging studies were evaluated by two radiologists in consensus. Location, size, and imaging features of primary tumors were recorded as well as the presence of recurrent disease and location of metastases. Results: Among 13 patients, 3 died during the timeframe of this study. Nine patients had primary tumor in the lower extremity, and average tumor size was 9.3 cm (range 3.3–18 cm). On MRI, primary tumors were hyperintense on T2, isointense to muscle on T1, and demonstrated peripheral/septal enhancement. Three patients had local recurrence and 12 had metastatic disease, with lung involvement being the most common. Tumor density on contrast enhanced CT ranged from 8.2 to 82.9 Hounsfield unit (HU). FDG-PET/CT imaging was performed in 3 patients. One patient had no FDG avid disease and 2 patients had metastatic disease with standard uptake values (SUV) of 2.8 and 7.4. The patient with intense FDG uptake demonstrated more solid appearing tumor burden and had the shortest survival. Conclusions: EMC is a rare tumor that often occurs in the lower extremities and frequently metastasizes to the lungs. Increased tumor density and increased FDG uptake may be related to more aggressive disease

Intrathoracic malignant peripheral nerve sheath tumors: imaging features and implications for management

Background: The aim of the study was to analyze the clinical and imaging characteristics of primary intrathoracic malignant peripheral nerve sheath tumors (MPNSTs). Patients and methods. In this institutional review board (IRB)-approved retrospective study, clinical and imaging features of 15 patients (eight men; mean age 50 years [range 18–83)] with pathologically proven malignant peripheral nerve sheath tumors seen from January 1999 to December 2011 were analyzed. Imaging features (CT in 15, MRI in 5 and PET/CT in 4) of primary tumors were evaluated by three radiologists and correlated with clinical management. Results: Of the 15 tumors, six were located in the mediastinum (two each in anterior, middle and posterior mediastinum), four in chest wall, two were paraspinal, and three in the lung. Four patients had neurofibromatosis-1 (NF1); four tumors had heterologous rhabdomyoblastic differentiation (malignant triton tumor). Masses typically were elongated along the direction of nerves, with mean size of 11 cm. The masses were hypo- or isodense to muscles on CT, isointense on T1-weighted images, hyperintense on T2-weighted images and intensely fluorodeoxyglucose (FDG) avid (mean standardized uptake value [SUV]max of 10.5 [range 4.4–23.6]). Necrosis and calcification was seen in four tumors each. Finding of invasion of adjacent structures on imaging led to change in management in seven patients; patients with invasion received chemoradiation. Conclusions: Intrathoracic MPNSTs appear as large elongated masses involving mediastinum, lung or chest wall. Radiological identification of invasion of adjacent structures is crucial and alters therapy, with patients with invasion receiving neoadjuvant or adjuvant chemoradiation

Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152621/1/cncr32508_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152621/2/cncr32508.pd

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

microsatellite data by locus and cohort

Microsatellite genotypes (genepop format) for all nine eastern oyster (Crassostrea virginica) hatchery cohorts (parents and offspring) from the publication. Alleles are represented in three digit format, missing data is represented by 000000

Data from: Tracking genetic diversity in a large-scale oyster restoration program: effects of hatchery propagation and initial characterization of diversity on restored vs. wild reefs

The release of hatchery-propagated fish and shellfish is occurring on a global scale, but the genetic impacts of these practices are often not fully understood and rarely monitored. Slow recovery of depleted eastern oyster populations in the Chesapeake Bay, USA has prompted a hatchery-based restoration program focused in the Choptank River, Maryland consisting of the mass release of hatchery-produced juveniles from local, wild broodstock. To evaluate potential genetic effects of this program, we 1) examined changes in genetic diversity (allelic richness, heterozygosity) and the effective number of breeders (Nb) over the hatchery production cycle with microsatellite-based parentage of natural, mass- and controlled-spawned cohorts, and 2) compared genetic diversity and effective population size (Ne) of a restored reef to wild source populations. Mass-spawned cohorts showed high variance in reproductive contribution, particularly among males, leading to a 45% average reduction in Nb from spawning adult numbers and higher relatedness–lower magnitude reductions in heterozygosity and significant reductions in allelic richness were also observed. While controlled-spawns (single male fertilizations of pooled eggs) reduced male variance, overall reproductive variance (Vk) remained high. Finally, oysters sampled from a restored reef displayed comparable Ne, genetic diversity, and relatedness to samples from wild populations, with no significant genetic differentiation among them. Overall, the hatchery-based results and initial field-based population genetic analyses suggest that despite reductions in diversity from parents to offspring due to high Vk, enhancement with rotated, wild broodstock appears to have maintained genetic diversity in a restored reef population compared to proximal wild populations