Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024
Genomic drivers in craniopharyngiomas: Analysis of the AACR project GENIE database.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Lehrich M Brandon, Tong C L Charles, Hsu P K Frank, Kuan C Edward
Аннотация
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.
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.