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Research into the DNA damage response (DDR) was recently honoured by the Nobel Prize in Chemistry and the Lasker Award. In this Timeline article, the authors provide a historical perspective on our understanding of the role of the DDR in cancer.
Since the Philadelphia chromosome was discovered in 1960, studies over the past six decades have identified fusion genes, oncogenes that provide great diagnostic and therapeutic advantages because of their tumour-specific expression. This Timeline article revisits the spectrum of gene fusions in cancer and how the methods to identify them have evolved, and also discusses the implications of current, sequencing-based approaches for detection.
Lynch syndrome is caused by heterozygous mutations and epimutations in mismatch repair genes, which lead to specific pathologies, including increased risk of multiple types of cancer and microsatellite instability. Lynch syndrome has been pivotal to the history of understanding hereditary cancer-prone syndromes and continues to lead the way in our understanding of the risk and treatment of familial cancers.
