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Adamantinomatous And Papillary Craniopharyngiomas Are Characterized By Distinct Epigenomic As Well As Mutational And Transcriptomic Profiles

A. Hoelsken, M. Sill, J. Merkle, L. Schweizer, M. Buchfelder, J. Flitsch, R. Fahlbusch, M. Metzler, M. Kool, S. Pfister, A. von Deimling, D. Capper, D. Jones, R. Buslei
Published 2016 · Biology, Medicine

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Introduction Craniopharyngiomas (CP) are rare epithelial tumors of the sellar region. Two subtypes, adamantinomatous (adaCP) and papillary CP (papCP), were previously identified based on histomorphological and epidemiological aspects. Recent data indicates that both variants are defined by specific genetic alterations, and influenced by distinct molecular pathways and particular origins. The fact that CP is an uncommon tumor entity renders studies on large cohorts difficult and exceptional. In order to achieve further insights distinguishing CP variants, we conducted whole genome methylation (450 k array) and microarray-based gene expression studies in addition to CTNNB1 and BRAF mutation analysis using a comprehensive cohort of 80 adaCP and 35 papCP.ResultsBRAFV600E mutations were solely found in the papCP subgroup and were not detectable in adaCP samples. In contrast, CTNNB1 mutations were exclusively detected in adaCP. The methylome fingerprints assigned DNA specimens to entity-specific groups (papCP (n = 18); adaCP (n = 25)) matching perfectly with histology-based diagnosis, suggesting that they represent truly distinct biological entities. However, we were not able to detect within the adaCP group (including 11 pediatric and 14 adult cases) a significant difference in methylation signature by age. Integrative comparison of the papCP with the adaCP group based on differential gene expression and methylation revealed a distinct upregulation of Wnt- and SHH signaling pathway genes in adaCP.ConclusionsAdaCP and papCP thus represent distinct tumor subtypes that harbor mutually exclusive gene mutations and methylation patterns, further reflected in differences in gene expression. This study demonstrates that DNA methylation analyses are an additional method to classify CP into subtypes, and implicates a role of epigenetic mechanisms in the genesis of the respective CP variants. Detection of tumor-specific signaling pathway activation enables the possibility of target-oriented intervention.
This paper references
Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up.
H. Müller (2011)
Handb Clin Neurol
Hl Muller (2014)
Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome.
H. Weiner (1994)
A tumor-specific cellular environment at the brain invasion border of adamantinomatous craniopharyngiomas
S. Burghaus (2009)
M. Garnett (2007)
Identification of targets for rational pharmacological therapy in childhood craniopharyngioma
J. Gump (2015)
Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans
C. Gaston-Massuet (2011)
Insights into the Infiltrative Behavior of Adamantinomatous Craniopharyngioma in a New Xenotransplant Mouse Model
C. Stache (2015)
BRAF V600E mutation is a useful marker for differentiating Rathke’s cleft cyst with squamous metaplasia from papillary craniopharyngioma
J. Kim (2015)
Inhibition of mutated, activated BRAF in metastatic melanoma.
K. Flaherty (2010)
Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma
G. Schindler (2011)
Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma
K. Kato (2004)
Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth.
C. Stache (2014)
Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations.
S. Sekine (2002)
Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma
C. Andoniadou (2012)
Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples
L. Macconaill (2009)
The classification of tumours of the central nervous system.
R. O. Barnard (1982)
BRAF V600E Mutations Are Common in Pleomorphic Xanthoastrocytoma: Diagnostic and Therapeutic Implications
D. Dias-Santagata (2011)
The 2007 WHO Classification of Tumours of the Central Nervous System
D. N. Louis (2007)
CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011.
Q. Ostrom (2014)
Chapter 16 - Craniopharyngioma
H. Müller (2014)
Consensus Clustering: A ResamplingBased Method for Class Discovery and Visualization of Gene Expression Microarray Data
S Monti (2003)
Nuclear β-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas
R. Buslei (2006)
Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling
A. Hoelsken (2010)
Short Communication Craniopharyngiomas of Adamantinomatous Type Harbor -Catenin Gene Mutations
S. Sekine (2002)
Analysis of the VNTR locus D1S80 by the PCR followed by high-resolution PAGE.
B. Budowle (1991)
BRAF V600E mutations are characteristic for papillary craniopharyngioma and may coexist with CTNNB1-mutated adamantinomatous craniopharyngioma
Sarah J. Larkin (2014)
The descriptive epidemiology of craniopharyngioma.
G. Bunin (1997)
Adamantinomatous craniopharyngioma: pathology, molecular genetics and mouse models
J. P. Martinez-Barbera (2015)
BRAF V600E analysis for the differentiation of papillary craniopharyngiomas and Rathke's cleft cysts
L. Schweizer (2015)
Predictive factors for craniopharyngioma recurrence: a systematic review and illustrative case report of a rapid recurrence.
R. Prieto (2013)
Endocrinol Metab Clin North Am
N Karavitaki (2008)
Target Gene Activation of the Wnt Signaling Pathway in Nuclear β‐Catenin Accumulating Cells of Adamantinomatous Craniopharyngiomas
A. Hoelsken (2009)
Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy.
P. Brastianos (2016)
Coexistence of adamantinomatous and squamous‐papillary type craniopharyngioma: Case report and discussion of etiology and pathology
Tomu Okada (2012)
Papillary craniopharyngioma: a clinicopathological study of 48 cases.
T. Crotty (1995)
Common mutations of β-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region
R. Buslei (2005)
Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential.
C. Andoniadou (2013)
Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody
D. Capper (2011)
Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1,195 cases from a single institution
S. Rosemberg (2005)
Childhood craniopharyngioma: current controversies on management in diagnostics, treatment and follow-up
H. Müller (2010)
Nuclear β-Catenin Accumulation as Reliable Marker for the Differentiation Between Cystic Craniopharyngiomas and Rathke Cleft Cysts: A Clinico-Pathologic Approach
B. Hofmann (2006)
Incidence of craniopharyngioma in Denmark (n = 189) and estimated world incidence of craniopharyngioma in children and adults
E. H. Nielsen (2011)
EGFR Signaling Regulates Tumor Cell Migration in Craniopharyngiomas
A. Hoelsken (2011)
Epidemiology and prognosis in children treated for intracranial tumours in Denmark 1960–1984
F. Gjerris (1998)
Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor
S. Aylwin (2015)
Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche?
A. Hoelsken (2013)
CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009.
T. A. Dolecek (2012)
Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation
S. Sekine (2004)
Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data
S. Monti (2004)
BRAF inhibition in refractory hairy-cell leukemia.
S. Dietrich (2012)
Craniopharyngiomas. Endocr Rev
N Karavitaki (2006)
Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.
M. García-Lavandeira (2012)
Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas
P. Brastianos (2014)

This paper is referenced by
Gene expression profiles reveal key genes for early diagnosis and treatment of adamantinomatous craniopharyngioma
J. Yang (2018)
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T. Goschzik (2017)
Preclinical transgenic and patient‐derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma
Jessica K. R. Boult (2018)
University of Birmingham The medical therapy of craniopharyngiomas
K. Alexandraki (2019)
Value of magnetic resonance imaging in predicting BRAF mutation in craniopharyngiomas
M. Giordano (2019)
Genetically modified mouse models of adamantinomatous craniopharyngioma
C. Andoniadou (2017)
TREM-1 expression in craniopharyngioma and Rathke's cleft cyst: its possible implication for controversial pathology
Y. Liu (2016)
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R. Jastania (2020)
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C. Gomes (2019)
Adult Craniopharyngiomas: Differences and Lessons from Paediatrics
Emmanuel Jouanneau (2020)
Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology
A. Hoelsken (2018)
The Inflammatory Milieu of Adamantinomatous Craniopharyngioma and Its Implications for Treatment
Ros Whelan (2020)
Leveraging the Role of the Metastatic Associated Protein Anterior Gradient Homologue 2 in Unfolded Protein Degradation: A Novel Therapeutic Biomarker for Cancer
Reem Alsereihi (2019)
Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma
S. Coy (2018)
Craniopharyngioma: a roadmap for scientific translation.
Saksham Gupta (2018)
Is gross total resection reasonable in adults with craniopharyngiomas with hypothalamic involvement ?
C. Apra (2019)
Adolescents and young adults with brain tumors in the context of molecular advances in neuro‐oncology
M. Zapotocky (2018)
Investigating the Protein Signature of Adamantinomatous Craniopharyngioma Pediatric Brain Tumor Tissue: Towards the Comprehension of Its Aggressive Behavior
C. Martelli (2019)
Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics.
Leslie C. Robinson (2016)
Expression of SRY-related HMG Box Transcription Factors (Sox) 2 and 9 in Craniopharyngioma Subtypes and Surrounding Brain Tissue
V. Thimsen (2017)
Biological Behaviour of Craniopharyngiomas
J. P. Martinez-Barbera (2020)
Recent advances in molecular pathology of craniopharyngioma [version 1; peer review: 2 approved]
Karavitaki (2019)
Pediatric craniopharyngioma in association with familial adenomatous polyposis
N. Dahl (2019)
Transcriptomic and Genomic Analyses of Human Craniopharyngioma
Leslie E Robinson (2017)
Low-grade epilepsy-associated neuroepithelial tumours — the 2016 WHO classification
I. Blümcke (2016)
Adamantinomatous Craniopharyngioma: Genomics, Radiologic Findings, Clinical, and Prognosis
H. Müller (2019)
Stem/progenitor cells in pituitary organ homeostasis and tumourigenesis
S. Haston (2018)
Noninvasive molecular diagnosis of craniopharyngioma with MRI-based radiomics approach
X. Chen (2019)
Drug priming enhances radiosensitivity of adamantinomatous craniopharyngioma via downregulation of survivin.
C. Stache (2016)
Rathke's Cleft Cyst as Origin of a Pediatric Papillary Craniopharyngioma
Sven-Martin Schlaffer (2018)
Distinct patterns of primary and motile cilia in Rathke’s cleft cysts and craniopharyngioma subtypes
S. Coy (2016)
Global epigenetic profiling identifies methylation subgroups associated with recurrence-free survival in meningioma
Adriana Olar (2017)
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