13 research outputs found
Pathogenic Germline Variants in 10,389 Adult Cancers
We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants
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Engineering evaluation/cost analysis for decontamination at the St. Louis Downtown Site, St. Louis, Missouri
The US Department of Energy (DOE) is implementing a cleanup program for three groups of properties in the St. Louis, Missouri, area: the St. Louis Downtown Site (SLDS), the St. Louis Airport Site (SLAPS) and vicinity properties, and the Latty Avenue Properties, including the Hazelwood Interim Storage Site (HISS). The general location of these properties is shown in Figure 1; the properties are referred to collectively as the St. Louis Site. None of the properties are owned by DOE, but each property contains radioactive residues from federal uranium processing activities conducted at the SLDS during and after World War 2. The activities addressed in this environmental evaluation/cost analysis (EE/CA) report are being proposed as interim components of a comprehensive cleanup strategy for the St. Louis Site. As part of the Department's Formerly Utilized Sites Remedial Action Program (FUSRAP), DOE is proposing to conduct limited decontamination in support of proprietor-initiated activities at the SLDS, commonly referred to as the Mallinckrodt Chemical Works. The primary goal of FUSRAP activity at the SLDS is to eliminate potential environmental hazards associated with residual contamination resulting from the site's use for government-funded uranium processing activities. 17 refs., 3 figs., 5 tabs
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Use of process monitoring for verifying facility design of large-scale reprocessing plants
During the decade of the 1990s, the International Atomic Energy Agency (IAEA) faces the challenge of implementing safeguards in large, new reprocessing facilities. The Agency will be involved in the design, construction, checkout and initial operation of these new facilities to ensure effective safeguards are implemented. One aspect of the Agency involvement is in the area of design verification. The United States Support Program has initiated a task to develop methods for applying process data collection and validation during the cold commissioning phase of plant construction. This paper summarizes the results of this task. 14 refs., 1 tab