Three-dimensional modelling and morphometric investigation of computed tomography images of brown bear’s (Ursus arctos) ossa cruris (Zeugopodium)

Background: This study was aimed to examine the detailed morphometrical and morphological characteristics of the bone by creating three-dimensional images through multidetector computed tomography images of ossa cruris in brown bears.Materials and methods: Four brown bear ossa cruris were used in the study.Results: It was observed that tibia and fibula articulated at proximal and distal epiphysis and they combined, and ossa cruris were shaped in this way. Cochlea tibiae were determined to be sagittally oriented. The length of the tibia was determined to be 268.97 mm and 266.32 mm at right and left sides, respectively. The length of the fibula was determined to be 249.16 mm and 250.19 mm on average at the right and left sides, respectively. In consequence of the correlation analysis, statistical relationships at different rates were detected between themeasured values.Conclusions: Detailed anatomical examinations are very important in terms of determining the similarities and differences of bear bones with those of the other species in the order Carnivora. Therefore, it is thought that this study will reveal detailed characteristics of ossa cruris of bears and provide data for further studies on archaeological and forensic sciences

Genomic basis for RNA alterations in cancer

Transcript alterations often result from somatic changes in cancer genomes. Various forms of RNA alterations have been described in cancer, including overexpression, altered splicing and gene fusions; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer

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

Genomic basis for RNA alterations in cancer.

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer

High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements

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

Rize bölge eğitim ve araşti{dotless}rma hastanesine başvuran kanser hastalari{dotless}ni{dotless}n tani{dotless} oranlari{dotless} ve Çernobil kazasi{dotless}ni{dotless}n etkileri

Objective: Chernobyl nuclear accident is world's one of the largest nuclear disasters ever. In neighboring countries the concerns for increased cancer rates appeared after the accident, and new studies were performed. Our area is among the places where radioactive particles have reached. Thus, we evaluated the regional cancer rates and the possible effects of the radiation. Material and Methods: Three thousand and five hundred cancer patients admitted to our hospital between January 2010 -July 2012 were included in the study. Their diagnosis were determined and percentage values were calculated. Women, men and general patient groups were compared with 2005 statistics of the Ministry of Health Department of Cancer Control. Results: In all groups; 20.2% breast cancer,13.5% lung cancer, 11.7% thyroid cancer, 7.4% colon cancer, 7.4% skin cancer were established. Thyroid cancer rates were higher compared to the country, and gender and age discriminations were made to investigate the reason. In male patients; 25.5% lung cancer, 12.2% prostate cancer, 9.3% colon cancer, 7.8% bladder cancer, 7.7% skin cancer were determined. The data are compatible with the entire country. In women; 38.9% breast cancer, 17.6% thyroid cancer, 7% skin cancer, 5.6% colon cancer, 5.3% leukemia were determined. Thyroid cancer rates were found higher and ages were analyzed:30.6% of them were under the age of 41, 69.4% were over the age of 41. Conclusion: Our region have similar cancer rates with the ones overall in Turkiye, but the rates of thyroid cancer in female patients were increased. Patients under the age of 15 years during the Chernobyl incident were not affected because the increase was seen in the elderly group. Nevertheless, detailed investigations with other factors should be entailed. © 2013 by Türkiye Klinikleri

The Diagnosis Rates of the Cancer Patients Referring to Rize Region Education and Research Hospital and Possible Effects of the Chernobyl Accident

Objective: Chernobyl nuclear accident is world's one of the largest nuclear disasters ever. In neighboring countries the concerns for increased cancer rates appeared after the accident, and new studies were performed. Our area is among the places where radioactive particles have reached. Thus, we evaluated the regional cancer rates and the possible effects of the radiation. Material and Methods: Three thousand and five hundred cancer patients admitted to our hospital between January 2010 -July 2012 were included in the study. Their diagnosis were determined and percentage values were calculated. Women, men and general patient groups were compared with 2005 statistics of the Ministry of Health Department of Cancer Control. Results: In all groups; 20.2% breast cancer,13.5% lung cancer, 11.7% thyroid cancer, 7.4% colon cancer, 7.4% skin cancer were established. Thyroid cancer rates were higher compared to the country, and gender and age discriminations were made to investigate the reason. In male patients; 25.5% lung cancer, 12.2% prostate cancer, 9.3% colon cancer, 7.8% bladder cancer, 7.7% skin cancer were determined. The data are compatible with the entire country. In women; 38.9% breast cancer, 17.6% thyroid cancer, 7% skin cancer, 5.6% colon cancer, 5.3% leukemia were determined. Thyroid cancer rates were found higher and ages were analyzed:30.6% of them were under the age of 41, 69.4% were over the age of 41. Conclusion: Our region have similar cancer rates with the ones overall in Turkiye, but the rates of thyroid cancer in female patients were increased. Patients under the age of 15 years during the Chernobyl incident were not affected because the increase was seen in the elderly group. Nevertheless, detailed investigations with other factors should be entailed. © 2013 by Türkiye Klinikleri