Mutational cascades in cancer

Mutational cascades in cancer

An Atlas of the Human Kinome Reveals the Mutational Landscape Underlying Dysregulated Phosphorylation Cascades in Cancer.

Kinase inhibitors are used widely to treat various cancers, but adaptive reprogramming of kinase cascades and activation of feedback loop mechanisms often contribute to therapeutic resistance. Determining comprehensive, accurate maps of kinase circuits may therefore help elucidate mechanisms of response and resistance to kinase inhibitor therapies. In this study, we identified and validated pho...

Signatures of mutational processes in human cancer

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 extractedmore than 20 distinct mutational signatures. Some are present ...

MuSiC: identifying mutational significance in cancer genomes.

Massively parallel sequencing technology and the associated rapidly decreasing sequencing costs have enabled systemic analyses of somatic mutations in large cohorts of cancer cases. Here we introduce a comprehensive mutational analysis pipeline that uses standardized sequence-based inputs along with multiple types of clinical data to establish correlations among mutation sites, affected genes a...

From Mutational Mechanisms in Single Cells to Mutational Patterns in Cancer Genomes.

Analysis of mutations in thousands of cancer genomes has revealed many characteristic patterns of mutagenesis. The search for the molecular mechanisms underlying these mutational patterns has not only generated novel biological insight but also led to the development of new experimental strategies to study cell-to-cell variation and genome evolution. In this essay, we discuss recent progress in...