Rachel Marty

Abstract Recent studies have characterized the extensive somatic alterations that arise during cancer. However, the somatic evolution of a tumor may be significantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specific tissues and alteration of specific cancer genes. Among germline–somatic interactions, we found germline variants in RBFOX1 that increased incidence of SF3B1 somatic mutation by 8-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants were associated with a 4-fold increased likelihood of somatic mutations in PTEN. In support of this association, we found that PTEN knockdown sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11. Finally, we observed that stratifying patients by germline polymorphisms exposed distinct somatic mutation landscapes, implicating new cancer genes. This study creates a validated resource of inherited variants that govern where and how cancer develops, opening avenues for prevention research. Significance: This study systematically identifies germline variants that directly affect tumor evolution, either by dramatically increasing alteration frequency of specific cancer genes or by influencing the site where a tumor develops. Cancer Discovery; 7(4); 410–23. ©2017 AACR. See related commentary by Geeleher and Huang, p. 354. This article is highlighted in the In This Issue feature, p. 339

Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing. In 1,078 TCGA breast cancer exomes, the fraction of CDR3 reads was associated with TILs fraction, tumor purity, adaptive immunity gene expression signatures and improved survival in Her2+ patients. Only 2/839 TCRB clonotypes were shared between patients and none associated with a specific HLA allele or somatic driver mutations. The iDNA biomarker enriches the comprehensive dataset collected through TCGA, revealing associations with other molecular features and clinical outcomes.

ABSTRACT Inland oil spills generally have received less attention than their coastal and marine counterparts. On the average, more than 2,000 spills occur on the inland waters of the continental United States each year. Recognizing the potential effects of these spills, the American Petroleum Institute has funded several studies in recent years to address issues associated with inland spills. One product of this activity is the preparation of a set of guidelines to be published as a manual for inland oil spill response. The manual focuses on the identification of techniques that would have minimal intrinsic ecological impacts (that is, to living resources) and would also minimize the total ecological and/or environmental impacts of the oil. The guidelines are intended to help decision makers assess whether the available response options can mitigate the effects of a spill and/or accelerate recovery from the oiling. The analysis and the recommendations are presented in a set of matrices that combine four oil types, more than 20 response techniques, and 10 inland freshwater habitats.

To assist the hydropower industry in better understanding potential future workforce, education and training needs and to help the U.S. Department of Energy (DOE) assess where to target future possible support efforts, the DOE selected Navigant Consulting, Inc. (Navigant) and the National Renewable Energy Laboratory (NREL) for a project with the following objectives1: Estimate the size of the current hydropower workforce in the United States, Catalog skills, training, and educational needs of the hydropower workforce and how those are met, Project the potential size of the hydropower workforce under different growth scenarios and where skillset gaps exist relative to today’s workforce, and Determine if additional training programs are needed to meet anticipated hydropower workforce needs in 2020 and 2030, and develop recommendations to fill the gaps. This paper outlines the project’s approach, analysis, findings, and recommendations.