OR01-03 DNA Copy Number Profiles In Recurrent And Stable Non-functioning Pituitary Adenomas

Abstract

Abstract Disclosure: G. Johannsson: None. M. Persson: None. S. Schlaffer: None. A. Fehr: None. C. Örndal: Employee; Self; Unilabs AB. W. Seager: None. M. Buchfelder: None. G. Stenman: None. D.S. Olsson: Consulting Fee; Self; Ipsen, Novo Nordisk, Sandoz. Grant Recipient; Self; Pfizer Global R&D. Employee; Self; AstraZeneca. Background: Residual tumors are common after primary surgery in patients with non-functioning pituitary adenoma (NFPA), 30-50% of these will experience tumor progression. Tumor control is of vital importance for patient outcome since tumor progression is strongly associated with excess morbidity and mortality. The aim of the study was to explore new potential biomarkers of tumor progression by studying the DNA copy number profiles of NFPAs with either a stable residual tumor behavior or marked tumor progression. Methods: In this case-controlled study, 72 patients operated for NFPA were selected. The progression group (n = 39) included patients [age at diagnosis (mean ± SD) 41.3±14.0 years] with marked tumor progression (30 patients required ≥3 surgical procedures). The stable group (n = 33; 61.1±10.2 years) had either a stable residual tumor without evidence of tumor progression during follow-up (n = 25) or no recurrence during follow-up (n = 8). The mean follow-up time in the stable group was 6.2 years (range 3.6-15 years). ArrayCGH analysis was performed on DNAs isolated from fresh frozen tumor tissue using the Human Genome CGH Microarray 244K and 180K oligonucleotide arrays. Copy number alterations (CNAs) were validated using FISH on formalin-fixed paraffin-embedded sections. Results: CNAs were identified in 29 tumors (40%). A total of 183 CNAs were detected in the 72 tumors, including 75 segmental alterations and 108 gains and losses of whole chromosomes and chromosome arms. The average number of CNAs per tumor was 2.5 (SD 5.9). CNAs were more common in the progression group compared to the stable group (Mean no. of CNAs 3.7 vs 1.2; P = 0.060). Twenty-four tumors (72%) in the stable group had normal profiles whereas only 19 (49%) in the progression group lacked CNAs. Eighteen CNAs were recurrent, defined as minimal common regions of deletion or gain in ≥4 tumors. The most frequently lost region was 11q21-q23.3 (n = 10). Deletions involving 10q23.21-q23.3 were seen in both the progression group (n = 5) and the stable group (n = 2) and included an approximately 2.8 Mb minimal common region harboring the tumor suppressor gene PTEN. The most frequent gains involved whole chromosomes 5 (n = 8), 7 (n = 10) and 12 (n = 7). Recurrent CNAs involving 10q (PTEN probe), 11q (MAML2 probe), and chromosomes 5 and 7 were confirmed using FISH. Conclusion: In this explorative study, we found a higher number of CNAs in NFPAs with marked tumor progression compared to stable adenomas without the need for reintervention during the long-term follow-up. Interestingly, segmental losses of chromosome 10q23.21-q23.3, including the tumor suppressor gene PTEN, were overrepresented in patients with marked tumor progression. Presentation: Thursday, June 15, 2023