Progestin-associated shift of meningioma mutational landscape

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