39 research outputs found
Author Correction: The landscape of viral associations in human cancers
Correction to: Nature Genetics https://doi.org/10.1038/s41588-019-0558-9, published online 05 February 2020
Sex differences in oncogenic mutational processes
Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research
Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing (Nature Genetics, (2020), 52, 3, (331-341), 10.1038/s41588-019-0576-7)
Correction to: Nature Genetics, published online 05 February 2020. In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper
Author Correction: Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
Correction to: Nature Genetics https://doi.org/10.1038/s41588-019-0564-y, published online 05 February 2020
Author Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers
Correction to: Nature Genetics, published online 05 February 2020. In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe
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
The relationship among restless legs syndrome (Willis–Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease
Spatial and temporal trends of the Stockholm Convention POPs in mothers’ milk — a global review
Scientific evidence underlying contraindications to the ketogenic diet: An update
First identified as a feasible treatment for intractable epilepsy, the ketogenic diet
(KD) has recently gained popularity thanks to growing evidence on applications such
as weight loss, most importantly, but also NAFLD, cancer, neurologic conditions and
chronic pain. As with any treatment, whether pharmacologic or not, the KD might
not be an appropriate intervention for every individual, and a number of contraindications
have been proposed, now deeply rooted into clinical practice, excluding de
facto many patients that could benefit from its use. However, many of these concerns
were expressed due to the absence of clinical studies conducted on fragile
populations, and an assessment of lately emerged evidence relative to KD safety is
currently lacking and much needed. We herein provide a critical revision of the literature
behind each safety alert, in order to guide through the treatment options in the
case of subjects with an indication to the KD and a borderline safe situation. Based
on available evidence, the possible use of this diet as a therapeutic intervention
should be assessed on a patient-to-patient basis by adequately skilled medical doctors,
keeping in mind current recommendations, but reading them through the knowledge
of the current state of the art