Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center.

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups

A CVD diamond beam telescope for charged particle tracking

Chemical vapor deposition (CVD) diamond is a radiation-hard sensor material that may be used for charged particle tracking near the interaction region in experiments at high-luminosity colliders. The goal of the work described in this paper is to investigate the use of several detector planes made of CVD diamond strip sensors for charged particle tracking. Toward this end, a tracking telescope composed entirely of CVD diamond planes has been constructed. The telescope was tested in muon beams, and its tracking capability has been investigated

Status ofthe R&D activity on diamond particle detectors

Chemical Vapor Deposited (CVD) polycrystalline diamond has been proposed as a radiation-hard alternative to silicon in the extreme radiation levels occurring close to the interaction region ofthe Large Hadron Collider. Due to an intense research effort, reliable high-quality polycrystalline CVD diamond detectors, with up to 270 mm charge collection distance and good spatial uniformity, are now available. The most recent progress on the diamond quality, on the development ofdiamond trackers and on radiation hardness studies are presented and discussed

Radiation tolerance of CVD diamond detectors for pions and protons

The paper gives new results on the radiation tolerance of CVD diamond for irradiation with 300 MeV/ c pions and 24 GeV/ c protons. The measured charge signal spectrum is compared at several irradiation levels with the spectrum calculated by a model. Irradiation by particles causes damage leading to a decrease of the charge signal. However, both the measurements and the outcome from the model show that for tracker applications this drawback is at least partly counterbalanced by a narrowing of the distribution curve of the charge signal. As a result, the efficiency of a CVD diamond tracker is less affected by irradiation than the mean charge signal