Abstract
Craniopharyngiomas are epithelial, sellar tumours comprising two subtypes: adamantinomatous (aCP) and papillary (pCP). The adamantinomatous form occurs predominantly during childhood whereas the papillary form is more common in adults. aCPs often contain mutations in CTNNB1, encoding β-catenin: a component of the adherens junction and mediator of Wnt signaling. The tumorigenic mechanism underlying pCPs is not well understood. In a large series of craniopharyngiomas we have shown that the adamantinomatous subtype harbours mutations in CTNNB1 in 44% of cases sequenced, while the papillary subtype has BRAF V600E mutations in 91% of cases sequenced, indicating that these lesions are genetically distinct with differing tumorigenic mechanisms, namely Wnt pathway (aCP) and MAPK pathway activation (pCP).
Immunohistochemically we have observed translocated β-catenin in 100% of aCPs, occurring not only in cell clusters but also in individual cells scattered throughout the tumour. Furthermore, there is no disruption of the adherens junction in these tumours. Immunohistochemistry staining for V600E was less reliable. Mutations in CTNNB1 and BRAF underlie tumorigenesis in the majority of craniopharyngiomas. The downstream effects of each of these pathways on tumorigenesis is yet to be elucidated.
The TERT gene encodes the protein component of telomerase, a ribonucleoprotein complex that catalyzes the repair of telomeres. The somatic reactivation of telomerase activity is an important event enabling abnormally proliferating cancer cells to avoid cellular senescence. Transactivation of the TERT gene is promoted by both the WNT and MAPK pathways, via the promoter binding of B-Catenin and ETS transcription factors, respectively. Furthermore, somatic mutations (C228T and C250T) that sensitize the TERT promoter to MAPK stimulation are the most frequent non-coding mutations in cancer.
Here, we sought to explore the relationship between WNT and MAPK signalling pathways and TERT expression in a craniopharyngioma cohort.
No disclosures
Immunohistochemically we have observed translocated β-catenin in 100% of aCPs, occurring not only in cell clusters but also in individual cells scattered throughout the tumour. Furthermore, there is no disruption of the adherens junction in these tumours. Immunohistochemistry staining for V600E was less reliable. Mutations in CTNNB1 and BRAF underlie tumorigenesis in the majority of craniopharyngiomas. The downstream effects of each of these pathways on tumorigenesis is yet to be elucidated.
The TERT gene encodes the protein component of telomerase, a ribonucleoprotein complex that catalyzes the repair of telomeres. The somatic reactivation of telomerase activity is an important event enabling abnormally proliferating cancer cells to avoid cellular senescence. Transactivation of the TERT gene is promoted by both the WNT and MAPK pathways, via the promoter binding of B-Catenin and ETS transcription factors, respectively. Furthermore, somatic mutations (C228T and C250T) that sensitize the TERT promoter to MAPK stimulation are the most frequent non-coding mutations in cancer.
Here, we sought to explore the relationship between WNT and MAPK signalling pathways and TERT expression in a craniopharyngioma cohort.
No disclosures
| Original language | English |
|---|---|
| Number of pages | 1 |
| Publication status | Published - 15 Nov 2015 |
| Externally published | Yes |
| Event | New Horizons Conference 2015 - , United Kingdom Duration: 10 Dec 2015 → 10 Dec 2015 |
Conference
| Conference | New Horizons Conference 2015 |
|---|---|
| Country/Territory | United Kingdom |
| Period | 10/12/15 → 10/12/15 |