M Peyre1, S Gaillard2, C de Marcellus3, M Giry4, F Bielle5, C Villa6, A L Boch7, H Loiseau8, B Baussart2, L Cazabat9, M L Raffin-Sanson9, M Sanson10, M Kalamarides11. 1. Department of Neurosurgery, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris; Sorbonne Universités, UPMC, Université Paris 6, Paris; UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, F-75013, Paris. 2. Department of Neurosurgery, Hôpital Foch, Suresnes. 3. Department of Endocrinology, Hôpital Ambroise Paré, APHP, Boulogne-Billancourt. 4. UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, F-75013, Paris. 5. Sorbonne Universités, UPMC, Université Paris 6, Paris; UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, F-75013, Paris; Department of Neuropathology, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris. 6. Department of Pathological Cytology and Anatomy, Hôpital Foch, Suresnes; Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Paris. 7. Department of Neurosurgery, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris. 8. Department of Neurosurgery, Hôpital Pellegrin, Bordeaux. 9. Department of Endocrinology, Hôpital Ambroise Paré, APHP, Boulogne-Billancourt; Inserm U1173, Université Versailles-Saint-Quentin, Montigny-Le-Bretonneux, France. 10. Sorbonne Universités, UPMC, Université Paris 6, Paris; UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, F-75013, Paris. 11. Department of Neurosurgery, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris; Sorbonne Universités, UPMC, Université Paris 6, Paris; UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, F-75013, Paris. Electronic address: michel.kalamarides@aphp.fr.
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.
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.
Authors: Maryam N Shahin; Stephen T Magill; Cecilia L Dalle Ore; Jennifer A Viner; Pamela N Peters; David A Solomon; Michael W McDermott Journal: J Neurooncol Date: 2019-03-13 Impact factor: 4.130
Authors: L di Filippo; S La Marca; M Losa; M S Lena; R Mapelli; G Incampo; P Mortini; F De Cobelli; A Giustina; R Lanzi Journal: J Endocrinol Invest Date: 2022-10-21 Impact factor: 5.467