COSMIC, the Catalogue Of Somatic Mutations In Cancer (https://cancer.sanger.ac.uk) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. The latest release, COSMIC v86 (August 2018), includes almost 6 million coding mutations across 1.4 million tumour samples, curated from over 26 000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations. COSMIC is primarily hand-curated, ensuring quality, accuracy and descriptive data capture. Building on our manual curation processes, we are introducing new initiatives that allow us to prioritize key genes and diseases, and to react more quickly and comprehensively to new findings in the literature. Alongside improvements to the public website and data-download systems, new functionality in COSMIC-3D allows exploration of mutations within three-dimensional protein structures, their protein structural and functional impacts, and implications for druggability. In parallel with COSMIC's deep and broad variant coverage, the Cancer Gene Census (CGC) describes a curated catalogue of genes driving every form of human cancer. Currently describing 719 genes, the CGC has recently introduced functional descriptions of how each gene drives disease, summarized into the 10 cancer Hallmarks.
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http://dx.doi.org/10.1093/nar/gky1015 | DOI Listing |
Mol Biol Evol
January 2025
Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array of endogenous and exogenous factors associated with somatic changes. However, the overall landscape of mutational processes in germline mutations across the tree of life and associated evolutionary driving forces are rather unclear. In this study, we analyzed mutational processes in single-stranded RNA (ssRNA) viruses which are known to jump between different hosts with divergent exogenous environments.
View Article and Find Full Text PDFFamilial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.
View Article and Find Full Text PDFNat Methods
January 2025
Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
In vivo lineage tracing holds great potential to reveal fundamental principles of tissue development and homeostasis. However, current lineage tracing in humans relies on extremely rare somatic mutations, which has limited temporal resolution and lineage accuracy. Here, we developed a generic lineage-tracing tool based on frequent epimutations on DNA methylation, enabled by our computational method MethylTree.
View Article and Find Full Text PDFAnn Hematol
January 2025
Hematology, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, 09121, Italy.
VEXAS syndrome is a complex hemato-inflammatory disorder, driven by somatic mutations in the UBA1 gene within hematopoietic precursor cells. It is characterized by systemic inflammation, rheumatological manifestations, and frequent association with myelodysplastic syndrome (MDS). We present a series of four VEXAS cases, all of which include concomitant MDS, each displaying distinct genetic signatures and clinical features at diagnosis, with a focus on their diagnostic and therapeutic implications.
View Article and Find Full Text PDFEpigenetics Chromatin
January 2025
Department of Molecular Biology, Semmelweis University, Budapest, Hungary.
DNA methylation, catalyzed by DNA methyltransferases (DNMT), plays pivotal role in regulating embryonic development, gene expression, adaption to environmental stress, and maintaining genome integrity. DNMT family consists of DNMT1, DNMT3A, DNMT3B, and the enzymatically inactive DNMT3L. DNMT3A and DNMT3B establish novel methylation patterns maintained by DNMT1 during replication.
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