Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
Nasopharyngeal carcinoma (NPC) is a complex disease involving Epstein-Barr virus (EBV) infection, genetic and environmental factors. To understand the molecular basis of NPC pathogenesis and identify the potential therapeutic targets, previously we carried out genomic and epigenomic studies to characterize the important molecular changes using whole-exome sequencing (WES), whole-genome bisulfite sequencing, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and Hi-C in NPC. In the integrative analysis, we identified several molecular subtypes associated with clinical outcomes and key cellular factors for regulatory epigenome for NPC. For example, in a total of 216 NPC cases from three genomics studies, we identified a new mutational signature relevant to the deficiency of the homologous recombination (HR) repair pathway (BRCAness) in a subset of NPC cases (29.6%). Survival analysis indicates that this mutational signature is significantly associated with shorter overall survival after adjustment for stage, gender and age and stratification by studies in NPC. We will utilize the state-of-the-art sequencing technology to further understand the impact of these molecular subtypes on tumour microenvironment and their translational values. The detailed functional role of the key cellular factors will be further investigated.
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