Heterozygous Tumor Suppressor Microenvironment in Cancer Development

Trends Cancer. 2019 Sep;5(9):541-546. doi: 10.1016/j.trecan.2019.07.004. Epub 2019 Aug 15.


Hereditary cancer syndromes are typically caused by mutations of a tumor suppressor gene that lead to the early development of multifocal benign neoplasms followed by their malignant progression. However, the term 'hereditary cancer syndrome' may be misleading, as a large subgroup of syndromes are characterized by highly penetrant benign tumors. The reason why these cardinal tumors rarely progress to malignancy has been an elusive question in cancer biology. In this opinion article, we propose a framework where a heterozygous tumor suppressor gene microenvironment has antagonistic roles in tumorigenesis, by accelerating development of benign tumors while restraining further progression to malignant cancers.

Keywords: MPNST; NF1; STK11; benign tumor; hereditary benign tumor syndromes; hereditary cancer; malignant peripheral nerve sheath tumor; neurofibroma; tumor microenvironment; tumor suppressor gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Disease Progression
  • Genes, Tumor Suppressor*
  • Humans
  • Mutation
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / pathology
  • Tumor Microenvironment / genetics*