Case report of a Li-Fraumeni syndrome-like phenotype with a de novo mutation in CHEK2

Medicine (Baltimore). 2016 Jul;95(29):e4251. doi: 10.1097/MD.0000000000004251.


Background: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date.

Methods: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing.

Results: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22:29091846, G->A, p.H371Y) was identified in CHEK2, a Li-Fraumeni syndrome causal gene. Examining the status of this novel mutation in the patient's healthy siblings revealed its de novo origin.

Conclusion: Our study reports the first case of Li-Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease.

MeSH terms

  • Checkpoint Kinase 2 / genetics*
  • China
  • Cross-Cultural Comparison
  • DNA Mutational Analysis*
  • Exome / genetics
  • Female
  • Germ-Line Mutation / genetics*
  • Humans
  • Li-Fraumeni Syndrome / diagnosis
  • Li-Fraumeni Syndrome / ethnology
  • Li-Fraumeni Syndrome / genetics*
  • Middle Aged
  • Phenotype*
  • Rare Diseases*


  • Checkpoint Kinase 2
  • CHEK2 protein, human