Figure 3
Representation of mutant clones in the bronchial epithelium. Coloured cylinders represent different cellular clones of recent origin in the airway epithelium, each containing cells that share the same somatic mutations. Such a clone (shown for the one in salmon at the bottom) may contain a mixture of cell types, such as differentiated secretory cells (shown with granules in the cytoplasm), ciliated cells (depicted with cilia at the outer surface) and unstratified basal cells (square shaped), all sitting on the basement membrane (line at the very bottom). Such a cellular arrangement is named pseudostratified columnar epithelium and is typical for the airways. Clone size may vary, but presumably lies in the sub-millimeter range, which is much smaller than the diameter and the length of a brush used in bronchoscopy (shown on the right). Consequently, a brush sample contains many different clones and the proportion of cells carrying the same somatic mutations is very small and falls below the detection limit. Successful somatic mutation calling requires sampling a smaller area (i.e. coming closer to the detection limit by harvesting a higher proportion of cells carrying the same somatic mutations) and/or sequencing to a higher read depth (i.e. lowering the detection limit).
