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APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development

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TLDR
The findings implicate APOBEC activity as a key driver of PIK3CA mutagenesis and HPV-induced transformation and suggest that reduced exposure to exogenous carcinogens in HPV+ HNSCC creates a selective pressure that favors emergence of tumors with APOBec-mediated driver mutations.
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Integrated genomic and molecular characterization of cervical cancer

TL;DR: The extensive molecular characterization of 228 primary cervical cancers is reported, one of the largest comprehensive genomic studies of cervical cancer to date, and novel significantly mutated genes in cervical cancer are identified, revealing new potential therapeutic targets for cervical cancers.
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Biological and Therapeutic Impact of Intratumor Heterogeneity in Cancer Evolution

TL;DR: The processes shaping the cancer genome are explored, placing these within the context of tumor evolution and their impact on intratumor heterogeneity and drug development.
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Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets

TL;DR: It is shown that environmental stress and alterations in DNA repair genes associate with distinct mutation spectra, and multiple novel mutated genes in PDA are identified, with select genes harbouring prognostic significance.
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Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy

TL;DR: The impact of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer is discussed and the challenges and opportunities presented for personalized anticancer therapy, as well as the expanding field of precision immunotherapy are assessed.
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APOBECs and virus restriction

TL;DR: The sensitivity of viruses that lack counterdefense measures highlights the need to develop APOBEC-enabling small molecules as a new class of anti-viral drugs.
References
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Journal ArticleDOI

Comprehensive molecular portraits of human breast tumours

Daniel C. Koboldt, +355 more
- 04 Oct 2012 - 
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Journal ArticleDOI

Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.

TL;DR: The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer, and the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.
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Signatures of mutational processes in human cancer

Ludmil B. Alexandrov, +84 more
- 22 Aug 2013 - 
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
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Mutational heterogeneity in cancer and the search for new cancer-associated genes

Michael S. Lawrence, +96 more
- 11 Jul 2013 - 
TL;DR: A fundamental problem with cancer genome studies is described: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds and the list includes many implausible genes, suggesting extensive false-positive findings that overshadow true driver events.
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Signatures of mutational processes in human cancer

Ludmil B. Alexandrov, +84 more
- 22 Aug 2013 - 

Mutational Processes Molding the Genomes of 21 Breast Cancers