Genome sequencing of normal cells reveals developmental lineages and mutational processes.
Behjati S., Huch M., van Boxtel R., Karthaus W., Wedge DC., Tamuri AU., Martincorena I., Petljak M., Alexandrov LB., Gundem G., Tarpey PS., Roerink S., Blokker J., Maddison M., Mudie L., Robinson B., Nik-Zainal S., Campbell P., Goldman N., van de Wetering M., Cuppen E., Clevers H., Stratton MR.
The somatic mutations present in the genome of a cell accumulate over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree, the number of divisions that each cell has undergone and the mutational processes that have been operative. Here we describe whole genomes of clonal lines derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal, demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.