8744 Genomic Variant Landscape In Aggressive & Treatment Resistant Prolactin-Secreting Tumors

Abstract Disclosure: D. Marrero-Rodríguez: None. K. Taniguchi-Ponciano: None. F. Martinez-Mendoza: None. E. Peña-Martinez: None. S. Vela-Patiño: None. S. Hinojosa-Alvarez: None. J. Hernandez-Perez: None. R. Chavez-Santoscoy: None. E. Sosa-Eroza: None. P.E. Espinosa Cardenas: None. M. Mercado: None. Pituitary tumors (PT) represent the second most frequent intracranial tumor and this neoplasm arises from adenohypophyseal cells. Prolactin-secreting tumor (PRL-tumors) are the most commonly neoplasm of the pituitary gland and arises from lactotrophs, and account for 50% of all pituitary tumors. Pituitary tumors are highly heterogeneous lesions and many of them are invasive in up to 45%, with up to 15% being clinically aggressive. Aggressive PRL-tumors are defined as invasive tumors with unusually rapid growth rate despite maximal tolerated dopamine agonist dose and requiring additional therapy and presenting multirecurrent potential. Predicting pituitary tumor behavior remains a challenge, therefore we performed whole exome sequencing to identify genomic variant landscape from aggressive and treatment-resistant prolactin-secreting pituitary tumors. Interestingly one tumor showed one hotspot mutation in splicing factor gene SF3B1 (c.C1873T:p.R625C), a second tumor showed an stop codon in SF3B1 (c.C496T:p.R166*). We then evaluated known hereditary-related pituitary tumor genes, identifying three patients with two different GNAS allelic variants the first one showed c.A3059G:p.N1020S and two tumors with c.C1307A:p.A436D variants. PRKAR1A gene did not showed any allelic variants in our cohort, while all tumors presented c.A1636G:p.T546A variant in MEN1 gene, in AIP gene allelic variant c.C682A:p.Q228K was present in all tumors. PAX6 gene is related to pituitary gland development and function, we found a deletion (c.980delA:p.K327Rfs*29) causing frameshift present in all tumors. The target coding-gene for cabergoline, first line of treatment, DRD2 di not showed any allelic variant. Also XRCC1 and ABCB1 genes, which are related to drug and therapy response showed c.A1196G:p.Q399R and c.T2887G:p.S963A allelic variants in 100% and 88% of tumors, respectively. Together this genomic landscape could represent higher risk to harbor aggressive non-responsive PRL secreting tumor. Presentation: 6/1/2024