Unraveling the lexicon of complex mutational phenomena in human cancers

Abstract

Although most mutations found in cancer genomes are randomly distributed, some form complex genomic patterns. Over the past 15 years, genomics studies have systematically uncovered multiple mutational phenomena, assigning several of them evocative Greek terms including kataegis, omikli, kyklonas, chromothripsis, chromoplexy, pyrgo, rigma and tyfonas. These phenomena are associated with distinct, often incompletely understood, molecular mechanisms and have important implications for tumor evolution and clinical outcomes. This Perspective provides a comprehensive lexicon of these mutational phenomena, addressing ambiguities in their definitions and mechanisms while highlighting their diversity, proposed origins and known associations with mutational processes, drug resistance and clinical outcomes. Alexandrov and colleagues summarize the current understanding of complex mutational phenomena in human cancers and their associations with therapy and clinical outcomes.