Deciphering Signatures of Mutational Processes Operative in Human Cancer

By Ludmil B. Alexandrov, S. Nik-Zainal, David C. Wedge, Peter J. Campbell, Michael R. Stratton. Cell Reports, 2013

1,186 citations recorded by the source corpus.

SUMMARY The genome of a cancer cell carries somatic mutations that are the cumulative consequences of the DNA damage and repair processes operative during the cellular lineage between the fertilized egg and the cancer cell. Remarkably, these mutational processes are poorly characterized. Global sequencing initiatives are yielding catalogs of somatic mutations from thousands of cancers, thus providing the unique opportunity to decipher the signatures of mutational processes operative in human cancer. However, until now there have been no theoretical models describing the signatures of mutational processes operative in cancer genomes and no systematic computational approaches are available to decipher these mutational signatures. Here, by modeling mutational processes as a blind source separation problem, we introduce a computational framework that effectively addresses these questions. Our approach provides a basis for characterizing mutational signatures from cancer-derived somatic mutational catalogs, paving the way to insights into the pathogenetic mechanism underlying all cancers.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ebeb9dcdacf844d2f34ddc5998c1aff34c166723

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Citations in the corpus

Tissue-specific mutation accumulation in human adult stem cells during life (2016, positive): “Using non-negative matrix factorization 12 , we extracted three mutational process signatures (Fig.”
Signatures of mutational processes in human cancer (2013, positive): “Beyond these known examples of DNA damage processed by transcription-coupled NER, other signatures show strong transcriptional strand bias (5, 8, 10, 12, 16).”
deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution (2016, background): “found that at least 200 whole genome samples were required to determine the signatures of 20 mutational processes [5].”
The landscape of genomic alterations across childhood cancers (2018, neutral): “…of tumour genomes, this is modelled as a system of matrices for signatures ( P ) and exposures ( E ) defining the observed mutational catalogue ( M ) 91 : De novo deciphering of signatures was done as described 91 based on the mutational catalogues of all cancer types and of the pan-cancer cohort.”
SomaticSignatures: inferring mutational signatures from single-nucleotide variants (2014, background): “Mutational signatures link observed somatic single nucleotide variants to mutation generating processes (Alexandrov et al., 2013a).”