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Series GSE185041 Query DataSets for GSE185041
Status Public on Oct 19, 2021
Title Genetic and epigenetic characterization of posterior pituitary tumors
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary lobe. 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 TERT promoter mutation. The second group (n=16) contained most GCTs and a subset of SCOs, which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances is 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, has low mutation rates and favorable outcome. The other two subtypes have SCO or PITUI histology but are separated 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 alterations that represent potential therapeutic targets.
 
Overall design Bisulphite converted tumor DNA of 47 patients were hybridised to the Illumina Infinium 450k or 850k Human Methylation Beadchip
 
Contributor(s) Schmid S, Capper D
Citation(s) 34661724
Submission date Sep 29, 2021
Last update date Nov 30, 2021
Contact name Simone Schmid
E-mail(s) simone.schmid@charite.de
Organization name Charité-Universitätsmedizin Berlin
Department Department of Neuropathology
Street address Charitéplatz 1
City Berlin
ZIP/Postal code 10117
Country Germany
 
Platforms (2)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
GPL23976 Illumina Infinium HumanMethylation850 BeadChip
Samples (47)
GSM5603766 Sample_1: GCT01
GSM5603767 Sample_2: GCT02
GSM5603768 Sample_3: GCT03
Relations
BioProject PRJNA767426

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE185041_Matrix_processed.xlsx 382.1 Mb (ftp)(http) XLSX
GSE185041_RAW.tar 587.0 Mb (http)(custom) TAR (of IDAT)
Processed data are available on Series record

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