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@ARTICLE{Schmid:177085,
      author       = {S. Schmid and D. A. Solomon and E. Perez and A. Thieme$^*$
                      and B. K. Kleinschmidt-DeMasters and C. Giannini and A.
                      Reinhardt$^*$ and S. L. Asa and O. Mete and D. Stichel$^*$
                      and C. Siewert$^*$ and C. Dittmayer and M. Hasselblatt and
                      W. Paulus and C. Nagel and P. Harter$^*$ and J. Schittenhelm
                      and J. Honegger and E. Rushing and R. Coras and S. M.
                      Pfister$^*$ and R. Buslei and A. Koch and A. Perry and D. T.
                      W. Jones$^*$ and A. von Deimling$^*$ and D. Capper$^*$ and
                      M. B. Lopes},
      title        = {{G}enetic and epigenetic characterization of posterior
                      pituitary tumors.},
      journal      = {Acta neuropathologica},
      volume       = {142},
      number       = {6},
      issn         = {1432-0533},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2021-02291},
      pages        = {1025-1043},
      year         = {2021},
      note         = {2021 Dec;142(6):1025-1043},
      abstract     = {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.},
      keywords     = {Brain tumor (Other) / Granular cell tumor (Other) /
                      Molecular neuropathology (Other) / Pituicytoma (Other) /
                      Posterior pituitary gland neoplasms (Other) / Spindle cell
                      oncocytoma (Other)},
      cin          = {BE01 / B300 / HD01 / FM01 / B062 / B360},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)FM01-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)B360-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34661724},
      doi          = {10.1007/s00401-021-02377-1},
      url          = {https://inrepo02.dkfz.de/record/177085},
}