Abstract
Pituitary tumours (PT) are formed in the pituitary gland, a small gland situated at the base of the brain. These tumours can be categorized according to their histological origin and hormone production. In surgical series, non-functioning PT are the commonest subtype, followed by functioning somatotroph and corticotroph tumours. Different somatic alterations have been implicated in the pathogenesis of these tumours and the objective of our study was to expand our previous new finding of KRAS pathogenic genetic variants in pituitary tumours. We conducted a digital polymerase chain reaction (PCR) analysis on formalin-fixed paraffin-embedded tissue blocks belonging to 189 patients. The results showed that, from the 184 pituitary tumours with good quality samples, 13 tumours (7.1%) presented mutant KRAS. The median age of the mutated group was 47 years old (range 19-77) and most patients with mutant KRAS tumours were from the female gender (61.5%, 8/13) and non-functioning subtype. For the first-time, mutant KRAS in corticotroph and somatotroph tumours were detected, and the variants showed low allele frequencies. In conclusion, we demonstrated that pituitary tumours might have mutant KRAS, and these data were not previously described probably due to lack of sensitivity of previous technologies. By identifying these variants, even at minimal levels, we open doors to a deeper understanding of the tumour microenvironment, clonal evolution and potential therapeutic targets.
Published Version
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