Activation of Wnt/β-catenin signalling by mutually exclusive FBXW11 and CTNNB1 hotspot mutations drives salivary gland basal cell adenoma - RNA
Wnt signalling must be 'just right' to promote tumour growth. Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours that can be difficult to distinguish from each other and other salivary gland tumour subtypes. Due to their rarity, the genomic profiles of BCA and BCAC have not been explored. Using whole-exome and transcriptome sequencing of BCA and BCAC cohorts, we identify a novel recurrent FBXW11 missense mutation (p.F517S) in BCA, that was mutually exclusive with the previously reported CTNNB1 p.I35T gain-of-functon (GoF) mutation. These driver events collectively accounted for 94% of BCAs. In vitro, mutant FBXW11 had a dominant negative affect, characterised by defective binding to β-catenin and the accumulation of β-catenin in cells. This was consistent with the nuclear expression of β-catenin observed in BCA cases harbouring the FBXW11 p.F517S mutation and activation of the Wnt/β-catenin pathway and defines a novel mechanism of Wnt pathway control. The genomic profiles of BCAC were distinct from BCA, with hotspot DICER1 and HRAS mutations and putative driver mutations affecting PI3K/AKT and NF-κB signalling pathway genes. A single BCAC, which may represent a malignant transformation of BCA, harboured the recurrent FBXW11 mutation. These findings have important implications for the diagnosis and treatment of BCA and BCAC, which, despite histopathologic overlap, may be unrelated entities.
- 68 samples
- DAC: EGAC00001000000
- Technology: Illumina NovaSeq 6000
- PUB DUO:0000019 (version: 2021-02-23)publication requiredThis data use modifier indicates that requestor agrees to make results of studies using the data available to the larger scientific community.
- US DUO:0000026 (version: 2021-02-23)user specific restrictionThis data use modifier indicates that use is limited to use by approved users.
- IS DUO:0000028 (version: 2021-02-23)institution specific restrictionThis data use modifier indicates that use is limited to use within an approved institution.
- GRU DUO:0000042 (version: 2021-02-23)general research useThis data use permission indicates that use is allowed for general research use for any research purpose.
Wellcome Trust Sanger Institute Cancer Genome Group Data Sharing Policy
Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
Study ID | Study Title | Study Type |
---|---|---|
EGAS00001007746 | Other |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.
ID | File Type | Size | Located in | |
---|---|---|---|---|
EGAF00008415573 | cram | 2.1 GB | ||
EGAF00008415575 | cram | 2.1 GB | ||
EGAF00008415576 | cram | 2.6 GB | ||
EGAF00008415579 | cram | 2.7 GB | ||
EGAF00008415580 | cram | 2.8 GB | ||
EGAF00008415581 | cram | 1.5 GB | ||
EGAF00008415582 | cram | 1.6 GB | ||
EGAF00008415584 | cram | 2.1 GB | ||
EGAF00008415585 | cram | 2.7 GB | ||
EGAF00008415586 | cram | 2.4 GB | ||
EGAF00008415587 | cram | 3.1 GB | ||
EGAF00008415588 | cram | 2.1 GB | ||
EGAF00008415589 | cram | 2.1 GB | ||
EGAF00008415590 | cram | 1.7 GB | ||
EGAF00008415591 | cram | 1.9 GB | ||
EGAF00008415592 | cram | 2.1 GB | ||
EGAF00008415593 | cram | 1.3 GB | ||
EGAF00008415594 | cram | 2.5 GB | ||
EGAF00008415595 | cram | 102.0 MB | ||
EGAF00008415596 | cram | 2.4 GB | ||
EGAF00008415597 | cram | 2.2 GB | ||
EGAF00008415598 | cram | 727.3 MB | ||
EGAF00008415599 | cram | 2.5 GB | ||
EGAF00008415600 | cram | 1.4 GB | ||
EGAF00008415601 | cram | 2.2 GB | ||
EGAF00008415602 | cram | 2.0 GB | ||
EGAF00008415605 | cram | 2.1 GB | ||
EGAF00008415606 | cram | 2.3 GB | ||
EGAF00008415608 | cram | 1.9 GB | ||
EGAF00008415627 | cram | 2.6 GB | ||
EGAF00008415628 | cram | 1.6 GB | ||
EGAF00008415629 | cram | 2.1 GB | ||
EGAF00008415630 | cram | 1.7 GB | ||
EGAF00008415631 | cram | 2.2 GB | ||
EGAF00008415632 | cram | 1.8 GB | ||
EGAF00008415634 | cram | 2.2 GB | ||
EGAF00008415635 | cram | 2.2 GB | ||
EGAF00008415636 | cram | 2.0 GB | ||
EGAF00008415637 | cram | 2.5 GB | ||
EGAF00008415638 | cram | 1.8 GB | ||
EGAF00008415639 | cram | 3.0 GB | ||
EGAF00008415641 | cram | 2.3 GB | ||
EGAF00008415642 | cram | 2.3 GB | ||
EGAF00008415643 | cram | 2.0 GB | ||
EGAF00008415644 | cram | 2.6 GB | ||
EGAF00008415645 | cram | 1.8 GB | ||
EGAF00008415646 | cram | 1.7 GB | ||
EGAF00008415647 | cram | 2.3 GB | ||
EGAF00008415648 | cram | 2.2 GB | ||
EGAF00008415649 | cram | 1.9 GB | ||
EGAF00008415650 | cram | 2.2 GB | ||
EGAF00008415651 | cram | 2.5 GB | ||
EGAF00008415652 | cram | 3.1 GB | ||
EGAF00008415654 | cram | 579.7 MB | ||
EGAF00008415655 | cram | 1.4 GB | ||
EGAF00008415656 | cram | 1.1 GB | ||
EGAF00008415657 | cram | 1.5 GB | ||
EGAF00008415658 | cram | 1.5 GB | ||
EGAF00008415659 | cram | 1.6 GB | ||
EGAF00008415660 | cram | 1.6 GB | ||
EGAF00008415661 | cram | 2.7 GB | ||
EGAF00008415662 | cram | 2.4 GB | ||
EGAF00008415663 | cram | 1.8 GB | ||
EGAF00008415664 | cram | 1.8 GB | ||
EGAF00008415665 | cram | 3.0 GB | ||
EGAF00008415666 | cram | 3.2 GB | ||
EGAF00008415667 | cram | 1.9 GB | ||
EGAF00008415668 | cram | 2.2 GB | ||
68 Files (140.0 GB) |