研究人员还估计了发现的突变与相关的克隆扩增大小的关系。令人惊奇的是，这些含有驱动突变（Driver Mutations）的克隆扩增的幅度比仅携带乘客突变（Passengar Mutation）的细胞相比高了大约50％。“这意味着你需要一个生长优势才能进行到下一个突变，但这种增长的优势并不是故事的全部内容。”据London’s Institute of Cancer Research的 Mel Greaves教授评论说，有癌症驱动突变克隆出现温和增长的优势至少有两个可能的解释。“可能你需要更多的驱动突变得到一个有力的克隆，即会变成癌症”他说。“另一种解释是，拥有这些突变的细胞类型是至关重要的。”因为皮肤细胞一直在改变，只有干细胞或祖细胞是持续不变的，才能癌变。
研究结果还引起了年龄对皮肤细胞影响的关注，包括癌驱动突变为什么可能会随着年龄而堆积，甚至加快。
HIGH BURDEN AND PERVASIVE POSITIVE SELECTION OF SOMATIC MUTATIONS IN NORMAL HUMAN SKIN
How somatic mutations accumulate in normal cells is central to understanding cancer development but is poorly understood. We performed ultradeep sequencing of 74 cancer genes in small (0.8 to 4.7 square millimeters) biopsies of normal skin. Across 234 biopsies of sun-exposed eyelid epidermis from four individuals, the burden of somatic mutations averaged two to six mutations per megabase per cell, similar to that seen in many cancers, and exhibited characteristic signatures of exposure to ultraviolet light. Remarkably, multiple cancer genes are under strong positive selection even in physiologically normal skin, including most of the key drivers of cutaneous squamous cell carcinomas. Positively selected mutations were found in 18 to 32% of normal skin cells at a density of ~140 driver mutations per square centimeter. We observed variability in the driver landscape among individuals and variability in the sizes of clonal expansions across genes. Thus, aged sun-exposed skin is a patchwork of thousands of evolving clones with over a quarter of cells carrying cancer-causing mutations while maintaining the physiological functions of epidermis.
