Genome-wide methylation profiling differentiates benign from aggressive and metastatic pituitary neuroendocrine tumors.

Autor: Jotanovic J; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden., Boldt HB; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Department of Pathology, Odense University Hospital, Odense, Denmark., Burton M; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.; Clinical Genome Center, University of Southern Denmark, Odense, Denmark., Andersen MS; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Department of Endocrinology, Odense University Hospital, Odense, Denmark., Bengtsson D; Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.; Department of Internal Medicine, Kalmar County Hospital, Kalmar, Sweden., Bontell TO; Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden., Ekman B; Department of Endocrinology in Linköping, Department of Internal Medicine in Norrköping, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden., Engström BE; Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden.; Department of Endocrinology and Diabetes, Uppsala University Hospital, Uppsala, Sweden., Feldt-Rasmussen U; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen, Denmark.; Institute of Clinical Medicine, Faculty of Health Research Sciences, Copenhagen University, Copenhagen, Denmark., Heck A; Section for Specialized Endocrinology, Oslo University Hospital, Oslo, Norway., Jakovcevic A; Department of Pathology and Cytology, University Hospital Center Zagreb, Zagreb, Croatia.; School of Medicine, University of Zagreb, Zagreb, Croatia., Jørgensen JOL; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark., Kraljevic I; School of Medicine, University of Zagreb, Zagreb, Croatia.; Department of Endocrinology, University Hospital Center Zagreb, Zagreb, Croatia., Kunicki J; Department of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Lindsay JR; Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK., Losa M; Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy., Loughrey PB; Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK.; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Maiter D; Department of Endocrinology and Nutrition, UCL, Cliniques Universitaires Saint-Luc, Brussels, Belgium., Maksymowicz M; Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Manojlovic-Gacic E; Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Pahnke J; Translational Neurodegeneration Research and Neuropathology Lab, Department of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway.; Section of Neuropathology Research, Department of Pathology, Clinics for Laboratory Medicine, Oslo University Hospital, Oslo, Norway., Petersenn S; ENDOC Center for Endocrine Tumors, Hamburg, Germany.; University of Duisburg-Essen, Essen, Germany., Petersson M; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Popovic V; Medical Faculty, University of Belgrade, Belgrade, Serbia., Ragnarsson O; Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden., Rasmussen ÅK; Department of Nephrology and Endocrinology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Reisz Z; Department of Clinical Neuropathology, King's College Hospital, NHS Foundation Trust, London, UK., Saeger W; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schalin-Jäntti C; Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.; University of Helsinki, ENDO-ERN (European Reference Network On Rare Endocrine Conditions), Helsinki, Finland., Scheie D; Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Terreni MR; Department of Pathology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy., Tynninen O; University of Helsinki, ENDO-ERN (European Reference Network On Rare Endocrine Conditions), Helsinki, Finland.; Department of Pathology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Whitelaw B; Department of Endocrinology, King's College Hospital, NHS Foundation Trust, London, UK., Burman P; Department of Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden., Casar-Borota O; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. olivera.casar-borota@igp.uu.se.; Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden. olivera.casar-borota@igp.uu.se.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2024 Nov 23; Vol. 148 (1), pp. 68. Date of Electronic Publication: 2024 Nov 23.
DOI: 10.1007/s00401-024-02836-5
Abstrakt: Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurrent somatic mutations have been identified, and epigenetic alterations and chromosomal rearrangements have not been explored in larger cohorts of aggressive and metastatic PitNETs. In this study, we performed genome-wide methylation analysis, including copy-number variation (CNV) calculations, on tumor tissue specimens from a large international cohort of 64 patients with aggressive (48) and metastatic (16) pituitary tumors. Twelve patients with non-invasive pituitary tumors (Knosp 0-2) exhibiting an indolent course over a 5 year follow-up served as controls. In an unsupervised hierarchical cluster analysis, aggressive/metastatic PitNETs clustered separately from benign pituitary tumors, and, when only specimens from the first surgery were analyzed, three separate clusters were identified: aggressive, metastatic, and benign PitNETs. Numerous CNV events affecting chromosomal arms and whole chromosomes were frequent in aggressive and metastatic, whereas benign tumors had normal chromosomal copy numbers with only few alterations. Genome-wide methylation analysis revealed different CNV profiles and a clear separation between aggressive/metastatic and benign pituitary tumors, potentially providing biomarkers for identification of these tumors with a worse prognosis at the time of first surgery. The data may refine follow-up routines and contribute to the timely introduction of adjuvant therapy in patients harboring, or at risk of developing, aggressive or metastatic pituitary tumors.
(© 2024. The Author(s).)
Databáze: MEDLINE
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