Genomic drivers in craniopharyngiomas: Analysis of the AACR project GENIE database

Purpose Craniopharyngiomas are rare tumors originating in the sellar region, with limited information on their somatic mutational landscape. In this study, we utilized a publicly available genomic database to profile the somatic mutational landscape of craniopharyngioma patients and interrogate diff...

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Bibliographic Details
Published in:Child's nervous system 2024-06, Vol.40 (6), p.1661-1669
Main Authors: Lehrich, M. Brandon, Tong, C. L. Charles, Hsu, P. K. Frank, Kuan, C. Edward
Format: Article
Language:English
Subjects:
Adolescent
Adult
beta Catenin - genetics
Child
Child, Preschool
Cohort Studies
Craniopharyngioma - genetics
Databases, Genetic
Female
Genomics
Humans
Male
Medicine
Medicine & Public Health
Middle Aged
Mutation
Neurosciences
Neurosurgery
Pituitary Neoplasms - epidemiology
Pituitary Neoplasms - genetics
Young Adult
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Summary:Purpose Craniopharyngiomas are rare tumors originating in the sellar region, with limited information on their somatic mutational landscape. In this study, we utilized a publicly available genomic database to profile the somatic mutational landscape of craniopharyngioma patients and interrogate differences based on histologic subtype. Methods We utilized the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) ® database accessed from cBioPortal (v13.1-public) to query all patients with craniopharyngiomas. Results Of the 336 patients with sellar tumors, 51 (15.2%) had craniopharyngiomas. Of these 51 patients, 42 (82.4%) were adamantinomatous subtype and 9 (17.6%) were papillary subtype. In this cohort, 32 (62.7%) patients were pediatric, while 19 (37.3%) were adult. The top mutations in the cohort were: CTNNB1 (n = 37; 73%), BRAF (n = 7; 14%), ARID1B (n = 5; 10%), KMT2D (n = 4; 8%), FANCA (n = 4; 8%), ATM (n = 4; 8%), and TERT (n = 3; 8%). Of the 37 patients with CTNNB1 mutations, 8 (21.6%) had S33X, 9 (24.3%) had S37X, 7 (18.9%) had T41X, and 5 (13.5%) had D32X. In this cohort, CTNNB1 mutations tended to co-occur with ATM (n = 4; 10.8%), KMT2C (n = 4; 10.8%), TERT (n = 3; 8.1%), BLM (n = 3; 8.1%), and ERBB2/3 (n = 3; 8.1%), suggesting CTNNB1 mutations tended to co-occur with mutations in genes important in cell growth and survival, chromatin accessibility, and DNA damage response pathways. Conclusions CTNNB1 mutations account for a large proportion of somatic mutations in craniopharyngiomas. Identification of specific point mutations and secondary drivers may advance development of novel craniopharyngioma preclinical models for targeted therapy testing.
ISSN:0256-7040
1433-0350
DOI:10.1007/s00381-024-06320-z