Mechanisms underlying mutational signatures in human cancers

By Thomas Helleday, Saeed Eshtad, S. Nik-Zainal. Nature reviews genetics, 2014

793 citations recorded by the source corpus.

The collective somatic mutations observed in a cancer are the outcome of multiple mutagenic processes that have been operative over the lifetime of a patient. Each process leaves a characteristic imprint — a mutational signature — on the cancer genome, which is defined by the type of DNA damage and DNA repair processes that result in base substitutions, insertions and deletions or structural variations. With the advent of whole-genome sequencing, researchers are identifying an increasing array of these signatures. Mutational signatures can be used as a physiological readout of the biological history of a cancer and also have potential use for discerning ongoing mutational processes from historical ones, thus possibly revealing new targets for anticancer therapies.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/10f3a1c3375355d21d8b9cd44f6ad9e380467a4b

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Citations in the corpus

• Landscape of somatic mutations in 560 breast cancer whole genome sequences (2016, neutral): “Mutational processes generating somatic mutations imprint particular patterns of mutations on cancer genomes, termed signatures2,24,37.”
• Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas (2018, neutral): “…e.g., the short tandem repeat instability linked to the inactivation or silencing of DNA MMR in colorectal, ovarian, or endometrial cancer (Alexandrov et al., 2013; Helleday et al., 2014; Kass et al., 2016) The therapeutic implications of altered DDR function are becoming better known.”
• deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution (2016, background): “Thus, through studying the full landscape of mutations present in a tumor and identifying the genomic footprint of mutational signatures that have contributed to them, processes molding the cancer genome during evolution can be revealed and individual therapeutic strategies considered if distinct DN”
• Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. (2015, background): “Intriguingly, in many cases, the underlying etiology of these mutational signatures remains unknown (Helleday et al., 2014).”
• Repair Pathway Choices and Consequences at the Double-Strand Break (2015, neutral): “Despite our improved understanding of the genetic and molecular features of cancer cells, the association between tumor genomic features (such as HR deficiency) and clinically relevant endpoints (such as disease response and patient outcome) is not well established [100].”