ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)
Clinical exome sequencing study of growth hormone secreting pituitary tumors
Flavia Costanza 1 , Giovanni Luca Scaglione 2 , Filippo Russo 3 , Carmela Nardelli 3 , Marco Gessi 4 , Antonella Giampietro 1 , Pier Paolo Mattogno 5 , Liverana Lauretti 5 , Guido Rindi 4 , Laura De Marinis 1 , Antonio Bianchi 1 , Francesco Doglietto 5 , Alfredo Pontecorvi 1 , Sabrina Chiloiro 1 & Ettore Domenico Capoluongo 6
1Department of Medical and Surgical Translational Sciences, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; 2Bioinformatic Unit, Istituto Dermopatico dell’Immacolata (IDI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; 3Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy; 4Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; 5Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; 6Department of Clinical Pathology, San Giovanni-Addolorata Hospital, Rome, Italy
JOINT2447
The biological behaviour of growth hormone secreting pituitary tumors (GH-PitNETs) varies significantly and strongly influences prognosis. The tumor microenvironment (TME) may provide a useful framework for understanding this heterogeneous behaviour of GH-PitNETs, through the dynamic interplay between tumour cells and TME components. Despite the interest in TME in acromegaly has increased exponentially over the last few decades, there is limited elucidation of its mechanisms, particularly in relation to genes expression involved in TME regulation. GH-PitNETs may be associated with specific germline mutations, however the genetic and molecular landscape of GH-PitNETs has been partially explored. Therefore, the aim of this study was to investigate germline genetic variants in patients with acromegaly through clinical exome sequencing (CES) analysis and to explore a possible correlation with molecular and histological characteristics of GH-PitNETs, including TME immune cells. A retrospective, observational, single centre study was conducted. Forty-six patients diagnosed with acromegaly were included in this study. In this cohort 31 were females (67%) and mean age at diagnosis was 55 (±12.3) years. After DNA extraction, CES was performed and genomic alterations were detected, classified and filtered using a dedicated bioinformatics pipeline. We excluded benign and probably benign variants according to the ACMG criteria, and variants with a minor allele frequency of more than 0.05 in the international databases. The remaining variants were subjected to the ENSEMBL Impact classification. The Metascape database was employed to perform pathway enrichment analyses, based on Gene Ontology biological process and KEGG Pathway for the targets. In our cohort, CES analysis identified 5759 unique variants in patients with GH-PitNETs, but no predominant variants were found. However, our data suggested that 5 unique mutations in 5 different genes (KCNJ12, FANCD2, TRIOBP, SYN2, and TYRO3) may be correlated with some tumor characteristics, including ki67% (P-value = 0.03), and invasiveness of GH-PitNETs (P-value = 0.01), possibly through some implication in TME regulation. Moreover, this is the first study showing that genes (FANCD2, SPTA1, TYRO3, and ZNF335) of the "regulation of lymphocyte activation" pathway (GO:0051249) may regulate immune cells infiltration in GH-PitNETs. In particular, these gene alterations seemed to influence the number of CD68+ macrophages (P-value = 0.015) and the ratio of CD68+ macrophages to CD8+ T-lymphocytes (P-value = 0.014). In conclusion, this study provides, for the first time, a comprehensive analysis by CES of germline variants in a cohort of GH-PitNETs. These findings may contribute understanding of the genetic landscape of acromegaly.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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