Nature Communications (May 2022)

Mutational landscape of normal epithelial cells in Lynch Syndrome patients

  • Bernard C. H. Lee,
  • Philip S. Robinson,
  • Tim H. H. Coorens,
  • Helen H. N. Yan,
  • Sigurgeir Olafsson,
  • Henry Lee-Six,
  • Mathijs A. Sanders,
  • Hoi Cheong Siu,
  • James Hewinson,
  • Sarah S. K. Yue,
  • Wai Yin Tsui,
  • Annie S. Y. Chan,
  • Anthony K. W. Chan,
  • Siu Lun Ho,
  • Peter J. Campbell,
  • Inigo Martincorena,
  • Simon J. A. Buczacki,
  • Siu Tsan Yuen,
  • Suet Yi Leung,
  • Michael R. Stratton

DOI
https://doi.org/10.1038/s41467-022-29920-2
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 10

Abstract

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It is unclear whether somatic mutation rates are elevated in Lynch Syndrome (LS), which is the most common cause of hereditary colorectal cancer. Here, the authors use whole-genome sequencing and organoid cultures to show that normal tissues in LS patients are genomically stable, while ancestor cells of neoplastic tissues undergo multiple cycles of clonal evolution.