Prevalence of somatic SF3B1 R625H mutation in lactotroph tumours from a multi-centric cohort: A digital PCR based study

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ID: 317329
2026
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Abstract
OBJECTIVE: An SF3B1 (Somatic splicing factor 3B subunit 1) mutation has been associated with prolactin-secreting pituitary neuroendocrine tumours (PitNET) with increased proliferation, invasion, dopamine agonist resistance and reduced progression-free survival. DESIGN: We screened a multi-centric cohort of 127 patients with prolactin-secreting PitNET for the SF3B1R625H mutation using digital PCR. METHODS: A comparative analysis was conducted between wild-type and mutated tumours, assessing clinical parameters, including age at diagnosis, sex distribution, prolactin levels, tumour size, extent of invasion, recurrence, and response to dopamine agonists. RESULTS: Somatic SF3B1R625H mutation was found in 21/127 patients (17%), who were diagnosed at a younger age (p=0.04) and had larger tumour diameter (p=0.03). Patients who needed transcranial surgery had a higher mutation frequency in their tumour samples compared to the transsphenoidal group (p=0.01). The occurrence of mutation was similar in males and females. Preoperative and postoperative prolactin levels were comparable in patients with mutant and wild-type tumours. No associations were observed between mutation and tumour invasiveness, Ki-67 proliferation index, p53 expression, recurrence and dopamine agonist resistance. Hypopituitarism at presentation, visual deficits, number of surgeries and disease-free survival were not different between the groups. CONCLUSION: SF3B1 somatic mutation status in lactotroph tumours-as assessed by digital PCR technology-is associated with a younger age at diagnosis and larger tumour diameter. However, in our cohort it does not appear to associate with histological features, higher recurrence, treatment resistance, tumour invasiveness, or long-term outcomes in our multi-centric cohort.
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Authors Ashutosh Rai, Sayka Barry, Federica Mangili, Anna Maria Barbieri, Bálint Scheich, Donato Iacovazzo, Debojyoti Chatterjee, Thomas F. Rice, Federica Begalli, Federico Roncaroli, Kesson Magid, Oniz Suleyman, Nikolette Szücs, Judit Tõke, Aura D. Herrera‐Martínez, Alfonso Soto‐Moreno, Judith López‐Fernández, Miguel E. G-García, Raúl M. Luque, Federica Guaraldi, Diego Mazzatenta, Francesca Gentilini, Sofia Asioli, Alessandra Mangone, Marco Locatelli, Andrea Lania, Miklós Tóth, Pinaki Dutta, Giovanna Mantovani, Erika Peverelli, Márta Korbonits
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Journal european journal of endocrinology
Year 2026
DOI
10.1093/ejendo/lvag098
URL
https://doi.org/10.1093/ejendo/lvag098
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