Somatic evolutionary timings of driver mutations.

摘要: A unified analysis of DNA sequences from hundreds tumors concluded that the driver mutations primarily occur in earliest stages cancer formation, with relatively few mutation events detected late-arising subclones. However, emerging evidence sequencing multiple and tumor regions per individual suggests subclones additional are underestimated single-sample analyses. To test whether generally map to early development, we examined multi-regional data 101 individuals reported 11 published studies. Following previous studies, annotated as early-arising when all tumors/regions had those (ubiquitous). We then inferred fraction occurring compared it were found only single tumors/regions. While a large occurred cancers, later at least frequently drivers substantial number patients. This result was robust many different approaches annotate mutations. The relative frequency late varied among patients same type types. reports preponderance informed by variant allele profiles, which is challenging clearly distinguish between drivers. origin new not limited evolution, showing distinct and, consequently, characteristics. Therefore, extensive intratumor heterogeneity appear have newly acquired