Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Radiocarbon in Dissolved Organic and Inorganic Carbon From the Central North Pacific

From the 13th International Radiocarbon Conference held in Dubrovnik, Yugoslavia, June 20-25, 1988.Radiocarbon measurements are reported for dissolved organic carbon (DOC) and inorganic carbon (DIC) from seawater samples collected from the Alcyone-5 cruise in the central North Pacific Ocean in 1985. Differences between the UV-radiation techniques used here and those reported by Williams, Oeschger and Kinney (1969) to oxidize and recover the DOC from sea water are presented. UV unoxldizable DOC in these samples is discussed in a separate publication (Druffel, Williams & Suzuki,1989). We briefly discuss the penetration of the bomb 14C signal into the DOC and DIC pools. The temporal variability of Delta-14C in DIC in surface samples taken every 2-3 days is presented. Concentrations of total dissolved free (FAA) plus combined (hydrolyzable) amino acids (THAA) and total dissolved carbohydrates (TCHO) measured in the same water samples are also reported. Our main aim is to present the chemical and isotopic data from samples collected during the Alcyone-5 cruise. Detailed interpretation is published elsewhere.This material was digitized as part of a cooperative project between Radiocarbon and the University of Arizona Libraries.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Radiocarbon in dissolved organic and inorganic carbon from the central North Pacific

Radiocarbon measurements are reported for dissolved organic carbon (DOC) and inorganic carbon (DIC) from seawater samples collected from the Alcyone-5 cruise in the central North Pacific Ocean in 1985. Differences between the UV-radiation techniques used here and those reported by Williams, Oeschger and Kinney (1969) to oxidize and recover the DOC from sea water are presented. UV unoxldizable DOC in these samples is discussed in a separate publication (Druffel, Williams &amp; Suzuki,1989). We briefly discuss the penetration of the bomb 14C signal into the DOC and DIC pools. The temporal variability of z14C in DIC in surface samples taken every 2-3 days is presented. Concentrations of total dissolved free (FAA) plus combined (hydrolyzable) amino acids (THAA) and total dissolved carbohydrates TCHO) measured in the same water samples are also reported. Our main aim is to present the chemical and isotopic data from samples collected during the Alcyone-5 cruise. Detailed interpretation is published elsewhere

Radiocarbon in Dissolved Organic and Inorganic Carbon from the Central North Pacific

From the 13th International Radiocarbon Conference held in Dubrovnik, Yugoslavia, June 20-25, 1988.Radiocarbon measurements are reported for dissolved organic carbon (DOC) and inorganic carbon (DIC) from seawater samples collected from the Alcyone-5 cruise in the central North Pacific Ocean in 1985. Differences between the UV-radiation techniques used here and those reported by Williams, Oeschger and Kinney (1969) to oxidize and recover the DOC from sea water are presented. UV unoxldizable DOC in these samples is discussed in a separate publication (Druffel, Williams & Suzuki,1989). We briefly discuss the penetration of the bomb 14C signal into the DOC and DIC pools. The temporal variability of Delta-14C in DIC in surface samples taken every 2-3 days is presented. Concentrations of total dissolved free (FAA) plus combined (hydrolyzable) amino acids (THAA) and total dissolved carbohydrates (TCHO) measured in the same water samples are also reported. Our main aim is to present the chemical and isotopic data from samples collected during the Alcyone-5 cruise. Detailed interpretation is published elsewhere.This material was digitized as part of a cooperative project between Radiocarbon and the University of Arizona Libraries.The Radiocarbon archives are made available by Radiocarbon and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202