Carotenoid intake and adipose tissue carotenoid levels in relation to prostate cancer aggressiveness among African-American and European-American men in the North Carolina-Louisiana prostate cancer project (PCaP): Carotenoids and Prostate Cancer Aggressiveness

Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may be due to combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness

A Simplified Method to Distinguish Farmed (Salmo salar) from Wild Salmon: Fatty Acid Ratios Versus Astaxanthin Chiral Isomers

Mislabeling of farmed and wild salmon sold in markets has been reported. Since the fatty acid content of fish may influence human health and thus consumer behavior, a simplified method to identify wild and farmed salmon is necessary. Several studies have demonstrated differences in lipid profiles between farmed and wild salmon but no data exists validating these differences with government-approved methods to accurately identify the origin of these fish. Current methods are both expensive and complicated, using highly specialized equipment not commonly available. Therefore, we developed a testing protocol using gas chromatography (GC), to determine the origin of salmon using fatty acid profiles. We also compared the GC method with the currently approved FDA (United States Food and Drug Administration) technique that uses analysis of carotenoid optical isomers and found 100% agreement. Statistical validation (n = 30) was obtained showing elevated 18:2n-6 (z = 4.56; P = 0.0001) and decreased 20:1n-9 (z = 1.79; P = 0.07) in farmed samples. The method is suitable for wide adaptation because fatty acid methyl ester analysis is a well-established procedure in labs that conduct analysis of lipid composition and food constituents. GC analysis for determining the origin of North American salmon compared favorably with the astaxanthin isomer technique used by the FDA and showed that the fatty acid 18:2n-6 was the key indicator associated with the origin of these salmon

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

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

Determination of Vitamin a in Dried Human Blood Spots by High-Performance Capillary Electrophoresis with Laser-excited Fluorescence Detection

We have developed a high-performance capillary electrophoresis (HPCE) method to analyze the retinol (vitamin A) concentration as retinol-retinol binding protein (holo-RBP) from microvolumes of serum (5-10 µl) or one to two drops (~20 µl) of blood collected and air-dried on blood collection filter paper. A 0.64-cm diameter disk was cut from the dried whole blood specimens and the samples were dissolved in a pretreatment buffer and filtered. Filtrate was injected onto the HPCE column for analysis. The separation was carried out in a 60 cm x 50 µm I.D. fused-silica capillary and the running voltage was 20 kV. A He-Cd laser with a wavelength of 325 nm was used for excitation, and the fluorescence of the holo-RBP complex was monitored at 465 nm by a photodiode. A virtual linear relationship was obtained for the retinol concentrations between HPCE and HPLC for 28 serum samples, 19 dried venous blood samples and 9 capillary dried blood spot samples, indicating that valid measures of serum retinol can be obtained from one to two drops of capillary blood collected on filter paper. The absolute detection limit for retinol by HPCE is below 3 µg/l. The method is very useful for vitamin A level screening, especially for children and premature new-born babies

Fast Minimicroassay of Serum Retinol (Vitamin A) by Capillary Zone Electrophoresis with Laser-Excited Fluorescence Detection

In this paper, we present a fast minimicroassay of serum vitamin A by capillary zone electrophoresis with laser-excited fluorescence detection. A 60 cm x 50 µm I.D. fused-silica capillary was used for the separation, and the polymer coating was burned off 20 cm from the cathodic end to form a detection window. The buffer system consisted of 50 mM sodium phosphate plus 10 mM sodium chloride at pH 7.8. A helium-cadmium laser set at 325 nm was used for excitation, and the fluorescence of the vitamin A-retinol-binding protein complex was monitored at 465 nm using a photodiode. The stray and scattered radiation were removed by two special filters. Using this system, about 8 nl of serum sample were injected for direct analysis without any sample preparation. The analysis time for each sample was less than 6 min, and subfemtomole levels of vitamin A in human or animal blood could be easily detected. Therefore, the method is potentially useful for finger-prick vitamin A analysis, especially for babies and young children