Highlights d Molecular classes of PitNETs are identified by integrated pangenomic analyses d PitNETs molecular classification mainly reflects pituitary lineage, driven by PIT1 d Gonadotroph signatures are found in some corticotroph and somatotroph PitNETs d USP8-mutated corticotroph PitNETs correspond to a group with limited aggressiveness
Our results suggest that edited MRS is one of the most reliable tools to predict IDH mutation noninvasively, showing high sensitivity and specificity for 2HG detection. Integrating edited MRS in clinical practice may be highly beneficial for noninvasive diagnosis of glioma, prognostic assessment, and treatment planning.
This shift in mutational landscape indicates the vulnerability of certain meningeal cells and mutations to hormone-induced tumorigenesis. While the relationship between PIK3CA mutation frequency and hormone-related cancers such as breast and endometrial cancer is well-known, this hormonally induced mutational shift is a unique feature in molecular oncology.
Context
Aggressive pituitary tumours (APTs) are characterised by unusually rapid growth and lack of response to standard treatment. About 1-2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumours are overrepresented amongst APTs and PCs. Mutations in the ATRX gene, regulating chromatin remodelling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumours.
Objective
To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs.
Design
We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumours lacking ATRX immunolabeling, mutational status of the ATRX gene was explored.
Results
Nine of the 48 tumours (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18 - 28%) than in those with APTs (4/30 – 13%). Lack of ATRX was most common in the corticotroph tumours, 7/22 (32%), vs 2/24 (8%) in the tumours of the Pit-1 lineage. Loss-of-function ATRX mutations were found in all the nine ATRX immuno-negative cases: nonsense mutations (n=4), frameshift deletions (n=4) and large deletions affecting 22-28 of the 36 exons (n=3). More than one ATRX gene defect was identified in two PCs.
Conclusion
ATRX mutations occur in a subset of aggressive pituitary tumours and are more common in corticotroph tumours. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumours.
Our results confirmed that arachnoidolysis is an effective and safe treatment for posttraumatic syringomyelia. Because the majority of patients were stabilized, we concluded that surgery should be performed as soon as possible in patients with clearly progressing clinical features.
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