Patterns of chromosome 18 loss of heterozygosity in multifocal ileal neuroendocrine tumors

Genes Chromosomes Cancer. 2020 Sep;59(9):535-539. doi: 10.1002/gcc.22850. Epub 2020 Apr 27.


Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.

Keywords: chromosome 18; copy number variation; high-throughput sequencing; ileal neuroendocrine tumor; loss of heterozygosity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chromosomes, Human, Pair 18 / genetics*
  • DNA Copy Number Variations
  • Female
  • Humans
  • Ileal Neoplasms / genetics*
  • Ileal Neoplasms / pathology
  • Loss of Heterozygosity*
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / pathology