Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets

Prince, Eric; Whelan, Ros; Donson, Andrew M.; Staulcup, Susan; Hengartner, Astrid; Vijmasi, Trinka; Agwu, Chibueze; Lillehei, Kevin O.; Foreman, Nicholas; Johnston, James M.; Massimi, Luca; Anderson, Richard C. E.; Souweidane, Mark M.; Naftel, Robert P.; Limbrick, David D.; Grant, Gerald A.; Niazi, Toba; Dudley, Roy; Kilburn, Lindsay; Jackson, Eric M.; Jallo, George I.; Ginn, Kevin; Smith, Amy; Chern, Joshua J.; Lee, Amy; Drapeau, Annie; Krieger, Mark D.; Handler, Michael H.; Hankinson, Todd C.

doi:10.1186/s40478-020-00939-0

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…According to the theory of embryogenesis, CP may occur anywhere in the migration of Rathke's sac ( 1 ), such as the nasopharynx, paranasal sinus, third ventricle, and posterior cranial fossa ( 2 , 3 ). Still, it can also occur in the suprasellar cistern ( 4 ), temporal lobe ( 5 ), and cavernous sinus ( 6 ). This kind of ACP involving the anterior, middle, and posterior cranial fossa of adults is rarely reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

Craniopharyngioma involving the anterior, middle, and posterior cranial fossa in adults: A case report

Tian

et al. 2023

Front. Neurol.

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Craniopharyngioma (CP) is a rare benign tumor that develops from the residual epithelial cells of the craniopharynx, accounting for < 5% of intracranial tumors. It is common for CPs to grow in the sellar/parasellar region and extend suprasellar. The pathology classifies CPs into adamantinomatous craniopharyngiomas (ACP) and papillary craniopharyngiomas (PCP). The PCP is mainly solid and occurs only in adults. ACP is predominantly cystic and more common in childhood and adolescent. Multilocular cystic ACP involving the anterior, middle, and posterior cranial fossa is rare in adults. Here, we report a case of a 46-year-old adult male patient who presented with recurrent headaches for 1 year with choking and hoarseness. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple cystic masses in the anterior, middle, and posterior cranial fossa. Initial hypotheses included the following: CP, colloid cyst, enterogenous cyst, epidermoid cyst, and dermoid cyst. Subsequently, the patient underwent surgery and postoperative histopathology diagnosed ACP. Adults with ACP involving the anterior, middle, and posterior cranial fossae are uncommon. This is a rare condition that radiologists should be aware of.

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Section: Discussionmentioning

confidence: 99%

Craniopharyngioma involving the anterior, middle, and posterior cranial fossa in adults: A case report

Tian

et al. 2023

Front. Neurol.

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“…In addition, recent gene expression data indicate that therapeutic targets identified in pediatric ACP may also have relevance in adult ACP. 16 Thus, further investigations with larger patient numbers and additional agents are merited.…”

Section: Discussionmentioning

confidence: 99%

Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series

Prince¹,

Hoffman

Vijmasi³

et al. 2021

Journal of Neurosurgery: Case Lessons

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BACKGROUND Adamantinomatous craniopharyngioma (ACP) is a highly morbid adult and pediatric brain tumor derived from epithelial remnants of the craniopharyngeal canal (Rathke’s pouch), which gives rise to the anterior pituitary gland. Standard therapy includes maximal safe resection with or without radiation therapy. Systemic antitumor therapy remains elusive. Immune-related paracrine signaling involving the interleukin-6 receptor (IL-6R) may contribute to ACP pathogenesis. Tocilizumab, a recombinant humanized monoclonal antibody against IL-6R, is approved by the US Food and Drug Administration but does not cross an intact blood–brain barrier. OBSERVATIONS In a phase 0 trial design, a single dose of tocilizumab was delivered intravenously before clinically indicated surgical intervention in 3 children with ACP. The presence of tocilizumab was assayed in plasma, tumor tissue, tumor cyst fluid, and cerebrospinal fluid (n = 1) using a novel enzyme-linked immunosorbent assay. Tocilizumab reached ACP tumor tissue and/or cyst fluid after one systemic dose in every patient. LESSONS This finding helps explain extant data that indicate tocilizumab may contribute to ACP therapy. It further indicates that ACP does not reside behind an intact blood–brain barrier, dramatically broadening the range of potential antitumor therapies against this tumor. This has substantial implications for the design of future clinical trials for novel therapies against ACP in both children and adults.

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“…Furthermore, the latter classification does not clarify the relationship between different subtypes and dysregulated pathways. [18–20] Although heterogeneity is also significant among ACPs' transcriptome profiles in Prince et al 's [29] study, these authors failed to identify any differences between children and adults. However, a study of pediatric brain tumors identified two subtypes, "epithelial" and "immune hot," in ACPs by proteomics and phosphorylated proteomics data.…”

Section: Introductionmentioning

confidence: 99%

Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

Wang

Chuan

Lin

et al. 2023

Chinese Medical Journal

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Background: Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies. Methods: Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (83 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively. Results: Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial–mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group (P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB (P = 0.01). Conclusions: ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

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Transcriptional analyses of adult and pediatric adamantinomatous craniopharyngioma reveals similar expression signatures regarding potential therapeutic targets

Cited by 6 publications

References 13 publications

Craniopharyngioma involving the anterior, middle, and posterior cranial fossa in adults: A case report

Craniopharyngioma involving the anterior, middle, and posterior cranial fossa in adults: A case report

Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series

Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

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