Home > Publications database > Genetic and epigenetic characterization of posterior pituitary tumors. > print |
001 | 177085 | ||
005 | 20240229133731.0 | ||
024 | 7 | _ | |a 10.1007/s00401-021-02377-1 |2 doi |
024 | 7 | _ | |a pmid:34661724 |2 pmid |
024 | 7 | _ | |a 0001-6322 |2 ISSN |
024 | 7 | _ | |a 1432-0533 |2 ISSN |
024 | 7 | _ | |a altmetric:115408114 |2 altmetric |
037 | _ | _ | |a DKFZ-2021-02291 |
041 | _ | _ | |a English |
082 | _ | _ | |a 610 |
100 | 1 | _ | |a Schmid, Simone |0 0000-0002-5787-7343 |b 0 |
245 | _ | _ | |a Genetic and epigenetic characterization of posterior pituitary tumors. |
260 | _ | _ | |a Heidelberg |c 2021 |b Springer |
336 | 7 | _ | |a article |2 DRIVER |
336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1679063065_16993 |2 PUB:(DE-HGF) |
336 | 7 | _ | |a ARTICLE |2 BibTeX |
336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
500 | _ | _ | |a 2021 Dec;142(6):1025-1043 |
520 | _ | _ | |a Pituicytoma (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. |
536 | _ | _ | |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312) |0 G:(DE-HGF)POF4-312 |c POF4-312 |f POF IV |x 0 |
588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo01.inet.dkfz-heidelberg.de |
650 | _ | 7 | |a Brain tumor |2 Other |
650 | _ | 7 | |a Granular cell tumor |2 Other |
650 | _ | 7 | |a Molecular neuropathology |2 Other |
650 | _ | 7 | |a Pituicytoma |2 Other |
650 | _ | 7 | |a Posterior pituitary gland neoplasms |2 Other |
650 | _ | 7 | |a Spindle cell oncocytoma |2 Other |
700 | 1 | _ | |a Solomon, David A |0 0000-0003-4571-7999 |b 1 |
700 | 1 | _ | |a Perez, Eilis |b 2 |
700 | 1 | _ | |a Thieme, Anne |0 P:(DE-He78)21f693ba604e9286be3b25068b440d08 |b 3 |u dkfz |
700 | 1 | _ | |a Kleinschmidt-DeMasters, Bette K |b 4 |
700 | 1 | _ | |a Giannini, Caterina |b 5 |
700 | 1 | _ | |a Reinhardt, Annekathrin |0 P:(DE-He78)856d5c1d0205a79190ed88218ffaf9b2 |b 6 |u dkfz |
700 | 1 | _ | |a Asa, Sylvia L |b 7 |
700 | 1 | _ | |a Mete, Ozgur |b 8 |
700 | 1 | _ | |a Stichel, Damian |0 P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17 |b 9 |u dkfz |
700 | 1 | _ | |a Siewert, Christin |0 P:(DE-He78)f796c7ad2ee1221e915ff38c15557abd |b 10 |u dkfz |
700 | 1 | _ | |a Dittmayer, Carsten |b 11 |
700 | 1 | _ | |a Hasselblatt, Martin |b 12 |
700 | 1 | _ | |a Paulus, Werner |b 13 |
700 | 1 | _ | |a Nagel, Christoph |b 14 |
700 | 1 | _ | |a Harter, Patrick |0 P:(DE-He78)b15b56a6ed37417d476470c60c0140ff |b 15 |
700 | 1 | _ | |a Schittenhelm, Jens |b 16 |
700 | 1 | _ | |a Honegger, Jürgen |b 17 |
700 | 1 | _ | |a Rushing, Elisabeth |b 18 |
700 | 1 | _ | |a Coras, Roland |b 19 |
700 | 1 | _ | |a Pfister, Stefan M |0 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |b 20 |u dkfz |
700 | 1 | _ | |a Buslei, Rolf |b 21 |
700 | 1 | _ | |a Koch, Arend |b 22 |
700 | 1 | _ | |a Perry, Arie |b 23 |
700 | 1 | _ | |a Jones, David T W |0 P:(DE-He78)551bb92841f634070997aa168d818492 |b 24 |u dkfz |
700 | 1 | _ | |a von Deimling, Andreas |0 P:(DE-He78)a8a10626a848d31e70cfd96a133cc144 |b 25 |u dkfz |
700 | 1 | _ | |a Capper, David |0 P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c |b 26 |u dkfz |
700 | 1 | _ | |a Lopes, M Beatriz |0 0000-0001-8661-6727 |b 27 |
773 | _ | _ | |a 10.1007/s00401-021-02377-1 |0 PERI:(DE-600)1458410-4 |n 6 |p 1025-1043 |t Acta neuropathologica |v 142 |y 2021 |x 1432-0533 |
909 | C | O | |p VDB |o oai:inrepo02.dkfz.de:177085 |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 3 |6 P:(DE-He78)21f693ba604e9286be3b25068b440d08 |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 6 |6 P:(DE-He78)856d5c1d0205a79190ed88218ffaf9b2 |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 9 |6 P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17 |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 10 |6 P:(DE-He78)f796c7ad2ee1221e915ff38c15557abd |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 15 |6 P:(DE-He78)b15b56a6ed37417d476470c60c0140ff |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 20 |6 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 24 |6 P:(DE-He78)551bb92841f634070997aa168d818492 |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 25 |6 P:(DE-He78)a8a10626a848d31e70cfd96a133cc144 |
910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 26 |6 P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c |
913 | 1 | _ | |a DE-HGF |b Gesundheit |l Krebsforschung |1 G:(DE-HGF)POF4-310 |0 G:(DE-HGF)POF4-312 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Funktionelle und strukturelle Genomforschung |x 0 |
914 | 1 | _ | |y 2021 |
915 | _ | _ | |a Nationallizenz |0 StatID:(DE-HGF)0420 |2 StatID |d 2021-01-29 |w ger |
915 | _ | _ | |a DEAL Springer |0 StatID:(DE-HGF)3002 |2 StatID |d 2021-01-29 |w ger |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1190 |2 StatID |b Biological Abstracts |d 2021-01-29 |
915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2021-01-29 |
915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b ACTA NEUROPATHOL : 2019 |d 2021-01-29 |
915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |d 2021-01-29 |
915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |d 2021-01-29 |
915 | _ | _ | |a IF >= 10 |0 StatID:(DE-HGF)9910 |2 StatID |b ACTA NEUROPATHOL : 2019 |d 2021-01-29 |
920 | 1 | _ | |0 I:(DE-He78)BE01-20160331 |k BE01 |l DKTK BE zentral |x 0 |
920 | 1 | _ | |0 I:(DE-He78)B300-20160331 |k B300 |l KKE Neuropathologie |x 1 |
920 | 1 | _ | |0 I:(DE-He78)HD01-20160331 |k HD01 |l DKTK HD zentral |x 2 |
920 | 1 | _ | |0 I:(DE-He78)FM01-20160331 |k FM01 |l DKTK FM zentral |x 3 |
920 | 1 | _ | |0 I:(DE-He78)B062-20160331 |k B062 |l B062 Pädiatrische Neuroonkologie |x 4 |
920 | 1 | _ | |0 I:(DE-He78)B360-20160331 |k B360 |l Pediatric Glioma |x 5 |
980 | _ | _ | |a journal |
980 | _ | _ | |a VDB |
980 | _ | _ | |a I:(DE-He78)BE01-20160331 |
980 | _ | _ | |a I:(DE-He78)B300-20160331 |
980 | _ | _ | |a I:(DE-He78)HD01-20160331 |
980 | _ | _ | |a I:(DE-He78)FM01-20160331 |
980 | _ | _ | |a I:(DE-He78)B062-20160331 |
980 | _ | _ | |a I:(DE-He78)B360-20160331 |
980 | _ | _ | |a UNRESTRICTED |
Library | Collection | CLSMajor | CLSMinor | Language | Author |
---|