Browsing by Author "Heck, Ansgar (54684013300)"

In the original publication of this article, upper and lower part of Table 2 was incorrectly formatted. The incorrect and correct version of Table 2 are shown in this correction article. The original article has been corrected. Relevant significantly enriched gene sets associated with the DMPs that differed between aggressive and metastatic PitNETs in the first surgery specimens (upper table) and in the entire cohort (lower table) Hypermethylated and positive enriched in PC pval padj NES size KEGG cell adhesion molecules CAMS 6.26E-07 5.63E-05 1.65 122 KEGG axon guidance 6.51E-07 5.63E-05 1.65 122 KEGG pathways in cancer 1.43E-06 8.24E-05 1.44 313 KEGG neuroactive ligand receptor interaction 6.39E-06 0.00028 1.44 249 KEGG focal adhesion 7.16E-05 0.0015 1.44 191 KEGG adherens junction 8.97E-05 0.0017 1.64 67 KEGG calcium signaling pathway 0.00025 0.0039 1.40 166 KEGG leukocyte transendothelial migration 0.0019 0.019 1.43 108 KEGG ECM receptor interaction 0.0019 0.019 1.49 83 KEGG gap junction 0.0063 0.036 1.40 83 KEGG axon guidance 1.60E-06 0.00028 1.53 122 KEGG calcium signaling pathway 3.22E-06 0.00028 1.44 166 KEGG neuroactive ligand receptor interaction 0.00010 0.0045 1.31 249 KEGG regulation of actin cytoskeleton 0.00013 0.0045 1.34 197 KEGG MAPK signaling pathway 0.00030 0.0066 1.29 251 KEGG cell adhesion molecules cams 0.0018 0.035 1.33 122 KEGG ECM receptor interaction 0.0034 0.049 1.36 83 KEGG Wnt signaling pathway 0.0052 0.064 1.27 145 KEGG Hedgehog signaling pathway 0.0057 0.064 1.40 55 KEGG leukocyte transendothelial migration 0.011 0.10 1.28 108 Relevant significantly enriched gene sets associated with the DMPs that differed between aggressive and metastatic PitNETs in the first surgery specimens (upper part of the table) and in the entire cohort (lower part of the table) Hypermethylated and positive enriched in PC pval padj NES size KEGG Cell adhesion molecules CAMS 6.26E-07 5.63E-05 1.65 122 KEGG Axon guidance 6.51E-07 5.63E-05 1.65 122 KEGG Pathways in cancer 1.43E-06 8.24E-05 1.44 313 KEGG Neuroactive ligand receptor interaction 6.39E-06 0.00028 1.44 249 KEGG Focal adhesion 7.16E-05 0.0015 1.44 191 KEGG Adherens junction 8.97E-05 0.0017 1.64 67 KEGG Calcium signaling pathway 0.00025 0.0039 1.40 166 KEGG Leukocyte transendothelial migration 0.0019 0.019 1.43 108 KEGG ECM receptor interaction 0.0019 0.019 1.49 83 KEGG Gap junction 0.0063 0.036 1.40 83 Hypermethylated and positive enriched in PC pval padj NES size KEGG Axon guidance 1.60E-06 0.00028 1.53 122 KEGG Calcium signaling pathway 3.22E-06 0.00028 1.44 166 KEGG Neuroactive ligand receptor interaction 0.00010 0.0045 1.31 249 KEGG Regulation of actin cytoskeleton 0.00013 0.0045 1.34 197 KEGG MAPK signaling pathway 0.00030 0.0066 1.29 251 KEGG Cell adhesion molecules cams 0.0018 0.035 1.33 122 KEGG ECM receptor interaction 0.0034 0.049 1.36 83 KEGG Wnt signaling pathway 0.0052 0.064 1.27 145 KEGG Hedgehog signaling pathway 0.0057 0.064 1.40 55 KEGG Leukocyte transendothelial migration 0.011 0.10 1.28 108 © The Author(s) 2024.

In the original publication of this article, upper and lower part of Table 2 was incorrectly formatted. The incorrect and correct version of Table 2 are shown in this correction article. The original article has been corrected. Relevant significantly enriched gene sets associated with the DMPs that differed between aggressive and metastatic PitNETs in the first surgery specimens (upper table) and in the entire cohort (lower table) Hypermethylated and positive enriched in PC pval padj NES size KEGG cell adhesion molecules CAMS 6.26E-07 5.63E-05 1.65 122 KEGG axon guidance 6.51E-07 5.63E-05 1.65 122 KEGG pathways in cancer 1.43E-06 8.24E-05 1.44 313 KEGG neuroactive ligand receptor interaction 6.39E-06 0.00028 1.44 249 KEGG focal adhesion 7.16E-05 0.0015 1.44 191 KEGG adherens junction 8.97E-05 0.0017 1.64 67 KEGG calcium signaling pathway 0.00025 0.0039 1.40 166 KEGG leukocyte transendothelial migration 0.0019 0.019 1.43 108 KEGG ECM receptor interaction 0.0019 0.019 1.49 83 KEGG gap junction 0.0063 0.036 1.40 83 KEGG axon guidance 1.60E-06 0.00028 1.53 122 KEGG calcium signaling pathway 3.22E-06 0.00028 1.44 166 KEGG neuroactive ligand receptor interaction 0.00010 0.0045 1.31 249 KEGG regulation of actin cytoskeleton 0.00013 0.0045 1.34 197 KEGG MAPK signaling pathway 0.00030 0.0066 1.29 251 KEGG cell adhesion molecules cams 0.0018 0.035 1.33 122 KEGG ECM receptor interaction 0.0034 0.049 1.36 83 KEGG Wnt signaling pathway 0.0052 0.064 1.27 145 KEGG Hedgehog signaling pathway 0.0057 0.064 1.40 55 KEGG leukocyte transendothelial migration 0.011 0.10 1.28 108 Relevant significantly enriched gene sets associated with the DMPs that differed between aggressive and metastatic PitNETs in the first surgery specimens (upper part of the table) and in the entire cohort (lower part of the table) Hypermethylated and positive enriched in PC pval padj NES size KEGG Cell adhesion molecules CAMS 6.26E-07 5.63E-05 1.65 122 KEGG Axon guidance 6.51E-07 5.63E-05 1.65 122 KEGG Pathways in cancer 1.43E-06 8.24E-05 1.44 313 KEGG Neuroactive ligand receptor interaction 6.39E-06 0.00028 1.44 249 KEGG Focal adhesion 7.16E-05 0.0015 1.44 191 KEGG Adherens junction 8.97E-05 0.0017 1.64 67 KEGG Calcium signaling pathway 0.00025 0.0039 1.40 166 KEGG Leukocyte transendothelial migration 0.0019 0.019 1.43 108 KEGG ECM receptor interaction 0.0019 0.019 1.49 83 KEGG Gap junction 0.0063 0.036 1.40 83 Hypermethylated and positive enriched in PC pval padj NES size KEGG Axon guidance 1.60E-06 0.00028 1.53 122 KEGG Calcium signaling pathway 3.22E-06 0.00028 1.44 166 KEGG Neuroactive ligand receptor interaction 0.00010 0.0045 1.31 249 KEGG Regulation of actin cytoskeleton 0.00013 0.0045 1.34 197 KEGG MAPK signaling pathway 0.00030 0.0066 1.29 251 KEGG Cell adhesion molecules cams 0.0018 0.035 1.33 122 KEGG ECM receptor interaction 0.0034 0.049 1.36 83 KEGG Wnt signaling pathway 0.0052 0.064 1.27 145 KEGG Hedgehog signaling pathway 0.0057 0.064 1.40 55 KEGG Leukocyte transendothelial migration 0.011 0.10 1.28 108 © The Author(s) 2024.

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. © The Author(s) 2024.

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. © The Author(s) 2024.