Publications by authors named "M Hirst"
tp53 R217H and R242H mutant zebrafish exhibit dysfunctional p53 hallmarks and recapitulate Li-Fraumeni syndrome phenotypes.
Biochim Biophys Acta Mol Basis Dis
December 2024
Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with a highly penetrant cancer spectrum characterized by germline TP53 mutations. We characterized the first LFS zebrafish hotspot mutants, tp53 R217H and R242H (human R248H and R273H), and found these mutants exhibit partial-to-no activation of p53 target genes, have defective cell-cycle checkpoints, and display partial-to-full resistance to apoptosis, although the R217H mutation has hypomorphic characteristics. Spontaneous tumor development histologically resembling human sarcomas was observed as early as 6 months.
View Article and Find Full Text PDFThe long non-coding RNA (lncRNA), HAR1A is emerging as a putative tumour suppressor. In non-neoplastic brain cells, REST suppresses HAR1A expression. In gliomas REST acts as an oncogene and is a potential therapeutic target.
View Article and Find Full Text PDFArticle Synopsis
- ARID1A, a key part of the BAF chromatin remodeling complex and mutated in about 8% of cancers, shows highest mutation rates in clear cell ovarian carcinoma (CCOC), reaching over 50%.
- Current treatments for ARID1A-deficient cancers are limited, prompting research into genetic dependencies using CRISPR screening.
- The study identifies KEAP1 as a critical factor in ARID1A-deficient cells, where targeting KEAP1 leads to selective growth inhibition and worsens genome instability, highlighting a potential new therapeutic approach.
Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX fusion oncoprotein. SS18::SSX associates with mammalian BAF complexes suggesting deregulation of chromatin architecture as the oncogenic driver in this tumour type. To examine the epigenomic state of SyS we performed comprehensive multi-omics analysis on 52 primary pre-treatment human SyS tumours.
View Article and Find Full Text PDFRemote consultations in community mental health: A qualitative study of clinical teams.
J Psychiatr Ment Health Nurs
October 2024
Unlabelled: WHAT IS KNOWN ON THE SUBJECT?: Mental health care can be delivered remotely through video and telephone consultations. Remote consultations may be cheaper and more efficient than in person consultations.
What The Paper Adds To Existing Knowledge: Accessing community mental health care through remote consultations is perceived as not possible or beneficial for all service users.