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000177085 1001_ $$00000-0002-5787-7343$$aSchmid, Simone$$b0
000177085 245__ $$aGenetic and epigenetic characterization of posterior pituitary tumors.
000177085 260__ $$aHeidelberg$$bSpringer$$c2021
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000177085 500__ $$a2021 Dec;142(6):1025-1043
000177085 520__ $$aPituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.
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000177085 650_7 $$2Other$$aBrain tumor
000177085 650_7 $$2Other$$aGranular cell tumor
000177085 650_7 $$2Other$$aMolecular neuropathology
000177085 650_7 $$2Other$$aPituicytoma
000177085 650_7 $$2Other$$aPosterior pituitary gland neoplasms
000177085 650_7 $$2Other$$aSpindle cell oncocytoma
000177085 7001_ $$00000-0003-4571-7999$$aSolomon, David A$$b1
000177085 7001_ $$aPerez, Eilis$$b2
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000177085 7001_ $$aKleinschmidt-DeMasters, Bette K$$b4
000177085 7001_ $$aGiannini, Caterina$$b5
000177085 7001_ $$0P:(DE-He78)856d5c1d0205a79190ed88218ffaf9b2$$aReinhardt, Annekathrin$$b6$$udkfz
000177085 7001_ $$aAsa, Sylvia L$$b7
000177085 7001_ $$aMete, Ozgur$$b8
000177085 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b9$$udkfz
000177085 7001_ $$0P:(DE-He78)f796c7ad2ee1221e915ff38c15557abd$$aSiewert, Christin$$b10$$udkfz
000177085 7001_ $$aDittmayer, Carsten$$b11
000177085 7001_ $$aHasselblatt, Martin$$b12
000177085 7001_ $$aPaulus, Werner$$b13
000177085 7001_ $$aNagel, Christoph$$b14
000177085 7001_ $$0P:(DE-He78)b15b56a6ed37417d476470c60c0140ff$$aHarter, Patrick$$b15
000177085 7001_ $$aSchittenhelm, Jens$$b16
000177085 7001_ $$aHonegger, Jürgen$$b17
000177085 7001_ $$aRushing, Elisabeth$$b18
000177085 7001_ $$aCoras, Roland$$b19
000177085 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b20$$udkfz
000177085 7001_ $$aBuslei, Rolf$$b21
000177085 7001_ $$aKoch, Arend$$b22
000177085 7001_ $$aPerry, Arie$$b23
000177085 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b24$$udkfz
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000177085 7001_ $$00000-0001-8661-6727$$aLopes, M Beatriz$$b27
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