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Database (Oxford) 2020 01;2020

Tecnologico de Monterrey, Escuela de Medicina, Cátedra de Bioinformática, Morones Prieto No. 3000, Colonia Los Doctores, Monterrey, Nuevo León 64710, Mexico.

Hotspots, recurrently mutated DNA positions in cancer, are thought to be oncogenic drivers because random chance is unlikely and the knowledge of clear examples of oncogenic hotspots in genes like BRAF, IDH1, KRAS and NRAS among many other genes. Hotspots are attractive because provide opportunities for biomedical research and novel treatments. Nevertheless, recent evidence, such as DNA hairpins for APOBEC3A, suggests that a considerable fraction of hotspots seem to be passengers rather than drivers. Read More

Cell 2020 03 20;180(5):915-927.e16. Epub 2020 Feb 20.

Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06511, USA. Electronic address:

The dichotomous model of "drivers" and "passengers" in cancer posits that only a few mutations in a tumor strongly affect its progression, with the remaining ones being inconsequential. Here, we leveraged the comprehensive variant dataset from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) project to demonstrate that-in addition to the dichotomy of high- and low-impact variants-there is a third group of medium-impact putative passengers. Moreover, we also found that molecular impact correlates with subclonal architecture (i. Read More

Front Microbiol 2019 10;10:1575. Epub 2019 Jul 10.

Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

The fungal component of the intestinal microbiota of eight healthy subjects was studied over 12 months using metagenome survey and culture-based approaches. , , , , , , and were the most recurrent and/or dominant fungal genera, according to metagenomic analysis. The biodiversity of fungal communities was lower and characterized by greater unevenness, when compared to bacterial microbiome. Read More

J Immunother Cancer 2019 05 7;7(1):123. Epub 2019 May 7.

Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.

The progression of cancer requires mutational adaptation to permit unrestrained proliferation. A fraction of cancer mutations are oncogenic drivers, while others are putative 'passengers' that do not contribute to oncogenesis. However, altered peptides arising from passenger mutations may bind MHCs and activate non-self immunologic signals (i. Read More

Sci Rep 2019 01 22;9(1):263. Epub 2019 Jan 22.

Institute of Structural and Molecular Biology, University College London, Gower Street, London, WC1E 6BT, UK.

Tumour sequencing identifies highly recurrent point mutations in cancer driver genes, but rare functional mutations are hard to distinguish from large numbers of passengers. We developed a novel computational platform applying a multi-modal approach to filter out passengers and more robustly identify putative driver genes. The primary filter identifies enrichment of cancer mutations in CATH functional families (CATH-FunFams) - structurally and functionally coherent sets of evolutionary related domains. Read More