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2015, Science 350 (6265), 1175-1177
This essay provides a brief summary of the known signatures of mutational processes in human cancer.
2013 •
All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
Mutation research
Multiple mutations in human cancers1996 •
Increasing evidence indicates that most human cancers contain multiple mutations. The exact number of mutations, their origin, and types remain to be determined. An over-riding question is whether the multiple mutations that accumulate in cancers is rate-limiting for the carcinogenic process. In this review we consider the argument that the large numbers of mutations routinely reported in human cancers cannot be accounted for by the rate of spontaneous mutation observed in normal human cells. We will analyze different mechanisms that might account for the accumulation of mutations in cancer cells. We conclude that cancer cells are genetically unstable; i.e., they exhibit a mutator phenotype. The recent reports of microsatellite instability in a variety of human cancers have provided the first strong evidence for the presence of a mutator phenotype in human cancers. However, we still lack information about the relationship between microsatellite instability and mutations that allow c...
2020 •
Mutational processes in tumors leave tell-tale genomic signatures composed of “passenger” mutations and mutations that have quantifiable effects on the proliferation and survival of cancer cell lineages. We identify the contributions of mutational processes to each oncogenic variant, quantifying responsibility for origination of changes at oncogenic variant sites contributing to tumorigenesis in 23 cancer types. We demonstrate that the variants driving melanomas and lung cancers are predominantly attributable to the actionable, preventable, exogenous mutational processes of ultraviolet light and tobacco exposure, whereas gliomas and prostate adenocarcinomas are largely attributable to endogenous processes associated with aging. Preventable mutations associated with pathogen exposure and APOBEC activity account for a large proportion of the cancer effect within head and neck, bladder, cervical, and breast cancers. These attributions complement epidemiological approaches—revealing the...
Carcinogenesis
Understanding mutagenesis through delineation of mutational signatures in human cancerEach individual cell within a human body acquires a certain number of somatic mutations during a course of its lifetime. These mutations originate from a wide spectra of both endogenous and exogenous mutational processes that leave distinct patterns of mutations, termed mutational signatures, embedded within the genomes of all cells. In recent years, the vast amount of data produced by sequencing of cancer genomes was coupled with novel mathematical models and computational tools to generate the first comprehensive map of mutational signatures in human cancer. Up to date, >30 distinct mutational signatures have been identified, and etiologies have been proposed for many of them. This review provides a brief historical background on examination of mutational patterns in human cancer, summarizes the knowledge accumulated since introducing the concept of mutational signatures and discusses their future potential applications and perspectives within the field.
2018 •
ABSTRACTSomatic mutations in cancer genomes are caused by multiple mutational processes each of which generates a characteristic mutational signature. Using 84,729,690 somatic mutations from 4,645 whole cancer genome and 19,184 exome sequences encompassing most cancer types we characterised 49 single base substitution, 11 doublet base substitution, four clustered base substitution, and 17 small insertion and deletion mutational signatures. The substantial dataset size compared to previous analyses enabled discovery of new signatures, separation of overlapping signatures and decomposition of signatures into components that may represent associated, but distinct, DNA damage, repair and/or replication mechanisms. Estimation of the contribution of each signature to the mutational catalogues of individual cancer genomes revealed associations with exogenous and endogenous exposures and defective DNA maintenance processes. However, many signatures are of unknown cause. This analysis provid...
Aeneas in the Troas and Latium Regions: Mythology and Archaeology
Prince Aeneas of Dardanos His Position in Trojan Mythology and his reflections in Troy in Ancient Times2021 •
Aeneas, who was considered as the founding ancestor of the Romans, appears as one of the leading heroes of the Trojans in Homer's Iliad. His descendants extends from his father Anchises to the founding fathers of Troy, to his mother Aphrodite and the gods of Olympus. In the war that started with the attack of the Achaeans to the city of Troy, he joined the support to Troy as the prince of Dardanus with the Dardanians under his command. His achievements in the war made him one as one of the most important hero of the Trojan army after Hector in Iliad. He killed many Achaeans in the war and clashed with Diomedes and Achilles, the leading heroes of the Achaenas. Instead of attracting the anger of the Olympus gods like other Trojans, Aeneas was protected by Apollo and Poseidon, especially his mother Aphrodite, as the new founder of Troy at the end of the war. But by his mother destiny set him on a completely different path, and instead of being the founder of the new Troy, he became the founding father of a new nation far away in Italy. The return of Aeneas to Troy, who sailed to Italy with a handful of survivors after the fall of Troy, was thanks to the Romans, who believed that they were descended from him hundreds of years later. The Romans became rulers not only of this city but of all Asia Minor, just as the gods prophesied in the epic.
China Perspectives
Entexted Heritage: Calligraphy and the (Re)Making of a Tradition in Contemporary China2021 •
A Proteção da Pessoa Humana: Temas Emergentes
A Proteção da Pessoa Humana: Temas Emergentes2023 •
Independência. Memória e Historiografia
Brasil Paralelo: Restaurando a Pátria, Resgatando a História. A Independência entre Memórias Públicas e Usos do Passado2023 •
Journal of Early Childhood Education Research
Investigating RightStart Mathematics kindergarten instruction in Finland2024 •
2017 •
2020 •
Journal of Clinical Pharmacy and Therapeutics
Causality assessment of adverse drug reactions: comparison of the results obtained from published decisional algorithms and from the evaluations of an expert panel, according to different levels of imputability2003 •
2008 •
Choice Reviews Online
Kremlin capitalism: the privatization of the Russian economy1997 •
Journal of Communication and Religion
“Aren’t I a Woman(ist)”: The Spiritual Epistemology of Sojourner Truth2016 •
International journal of academic research in business & social sciences
Parenting Style, Self-Control and Peer Influence toward Students’ Misbehavior2023 •
Clinical Infectious Diseases
Why Child Health and Mortality Prevention Surveillance?2019 •