Progestin-associated shift of meningioma mutational landscape

Ann Oncol. 2018 Mar 1;29(3):681-686. doi: 10.1093/annonc/mdx763.

Abstract

Background: Meningiomas are the most common primary tumor of the central nervous system. The relationship between meningioma and progestins is frequently mentioned but has not been elucidated.

Patients and methods: We identified 40 female patients operated for a meningioma after long-term progestin therapy and performed targeted next generation sequencing to decipher the mutational landscape of hormone-related meningiomas. A published cohort of 530 meningiomas in women was used as a reference population.

Results: Compared with the control population of meningiomas in women, progestin-associated meningiomas were more frequently multiple meningiomas [19/40 (48%) versus 25/530 (5%), P < 10-12] and located at the skull base [46/72 (64%) versus 241/481 (50%), P = 0.03]. We found a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8] and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower frequency of NF2-related tumors compared with the control population of meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001].

Conclusion: This shift in mutational landscape indicates the vulnerability of certain meningeal cells and mutations to hormone-induced tumorigenesis. While the relationship between PIK3CA mutation frequency and hormone-related cancers such as breast and endometrial cancer is well-known, this hormonally induced mutational shift is a unique feature in molecular oncology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chlormadinone Acetate / adverse effects
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Cyproterone Acetate / adverse effects
  • DNA Mutational Analysis
  • Female
  • Humans
  • Megestrol Acetate / adverse effects
  • Meningeal Neoplasms / genetics*
  • Meningeal Neoplasms / pathology
  • Meningioma / genetics*
  • Meningioma / pathology
  • Middle Aged
  • Mutation
  • Progesterone Congeners / adverse effects*
  • Retrospective Studies
  • Young Adult

Substances

  • Progesterone Congeners
  • Chlormadinone Acetate
  • Cyproterone Acetate
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Megestrol Acetate