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

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 = .04) and had larger tumour diameter (P = .03). Patients who needed transcranial surgery had a higher mutation frequency in their tumour samples compared to the transsphenoidal group (P = .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 be associated with histological features, higher recurrence, treatment resistance, tumour invasiveness, or long-term outcomes in our multi-centric cohort.